59 results on '"Audrey Gros"'
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2. Integrative diagnosis of primary cutaneous large B-cell lymphomas supports the relevance of cell of origin profiling.
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Audrey Gros, Sarah Menguy, Victor Bobée, Océane Ducharme, Isabelle Cirilo Cassaigne, Béatrice Vergier, Marie Parrens, Marie Beylot-Barry, Anne Pham-Ledard, Philippe Ruminy, Fabrice Jardin, and Jean-Philippe Merlio
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Medicine ,Science - Abstract
Primary cutaneous large B-cell lymphomas (PCLBCL) represent a diagnostic challenge because they are classified as PCLBCL, leg type (PCLBCL, LT) or primary cutaneous follicle centre lymphoma, large cell (PCFCL, LC), which differ by prognosis and therapeutic requirement. Unclassified cases with discordant clinical presentations, morphologies, and immunophenotypes may be classified into the not otherwise specified (PCLBCL, NOS) category based on ancillary molecular analyses. Cell-of-origin profiling as germinal centre (GC) type or non-GC type by immunohistochemistry is not considered reproducible because of variable CD10 expression. In a series of 55 PCLBCL cases with > 80% large cells, we reported 21 PCFCL, LC cases as GC-type and 27 PCLBCL, LT as non-GC-type; 7 cases were considered PCLBCL, NOS. Here, we demonstrate the accuracy of molecular profiling of PCLBCL as GC or non-GC type using a reverse transcriptase multiplex ligation assay (RT-MLPA). RT-MLPA classified the seven PCLBCL, NOS cases in accordance with their mutational profile. An integrative principal component analysis confirmed the main criteria and the relevance of genomic profiling of PCFCL, LC as GC-derived, and PCLBCL, LT as non-GC-derived. Both the cell-of-origin classification of PCLBCL and the integrative analysis identified two clinically relevant subgroups according to overall survival, which may help to standardize PCLBCL diagnosis and patient management.
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- 2022
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3. The Need for a Consensus Next-generation Sequencing Panel for Mature Lymphoid Malignancies
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Pierre Sujobert, Yannick Le Bris, Laurence de Leval, Audrey Gros, Jean Philippe Merlio, Cedric Pastoret, Sarah Huet, Clémentine Sarkozy, Frédéric Davi, Mary Callanan, Catherine Thieblemont, David Sibon, Vahid Asnafi, Claude Preudhomme, Philippe Gaulard, Fabrice Jardin, Gilles Salles, and Elizabeth Macintyre
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2019
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4. TP53 alterations in primary and secondary Sézary syndrome: A diagnostic tool for the assessment of malignancy in patients with erythroderma.
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Audrey Gros, Elodie Laharanne, Marie Vergier, Martina Prochazkova-Carlotti, Anne Pham-Ledard, Thomas Bandres, Sandrine Poglio, Sabine Berhouet, Béatrice Vergier, Jean-Philippe Vial, Edith Chevret, Marie Beylot-Barry, and Jean-Philippe Merlio
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Medicine ,Science - Abstract
Recent massive parallel sequencing data have evidenced the genetic diversity and complexity of Sézary syndrome mutational landscape with TP53 alterations being the most prevalent genetic abnormality. We analyzed a cohort of 35 patients with SS and a control group of 8 patients with chronic inflammatory dermatoses. TP53 status was analyzed at different clinical stages especially in 9 patients with a past-history of mycosis fungoides (MF), coined secondary SS. TP53 mutations were only detected in 10 patients with either primary or secondary SS (29%) corresponding to point mutations, small insertions and deletions which were unique in each case. Interestingly, TP53 mutations were both detected in sequential unselected blood mononuclear cells and in skin specimens. Cytogenetic analysis of blood specimens of 32 patients with SS showed a TP53 deletion in 27 cases (84%). Altogether 29 out of 35 cases exhibited TP53 mutation and/or deletion (83%). No difference in prognosis was observed according to TP53 status while patients with secondary SS had a worse prognosis than patients with primary SS. Interestingly, patients with TP53 alterations displayed a younger age and the presence of TP53 alteration at initial diagnosis stage supports a pivotal oncogenic role for TP53 mutation in SS as well as in erythrodermic MF making TP53 assessment an ancillary method for the diagnosis of patients with erythroderma as patients with inflammatory dermatoses did not display TP53 alteration.
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- 2017
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5. Assessment of Liquid Biopsy in Primary Cutaneous Diffuse Large B-Cell Lymphoma–Leg Type
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Marie Guicheney, Océane Ducharme, Charline Caumont, Emilie Gerard, Léa Dousset, Marie Beylot-Barry, Jean-Philippe Merlio, Audrey Gros, and Anne Pham-Ledard
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Cell Biology ,Dermatology ,Molecular Biology ,Biochemistry - Published
- 2023
6. Patient-Derived Xenograft and Cell Line Models of Human Primary Cutaneous Diffuse Large B-Cell Lymphoma-Leg Type
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Martina Prochazkova-Carlotti, Audrey Gros, Elodie Richard, Floriane Cherrier, Elodie Laharanne, Yamina Idrissi, Camille Baron, Sandrine Poglio, Océane Ducharme, Sarah Menguy, Anne Pham-Ledard, Marie Beylot-Barry, Jean-Philippe Merlio, and Laurence Bresson-Bepoldin
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Cell Biology ,Dermatology ,Molecular Biology ,Biochemistry - Published
- 2022
7. Combined Reverse-Transcriptase Multiplex Ligation-Dependent Probe Amplification and Next-Generation Sequencing Analyses to Assign Unclassified BCL2/BCL6 Nonrearranged Small B-Cell Lymphoid Neoplasms as Follicular or Nodal Marginal Zone Lymphoma
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Come Sesboue, Jean Galtier, Marie Jeanneau, Annick Chauvel, Elodie Laharanne, Samuel Amintas, Jean-Philippe Merlio, Krimo Bouabdallah, François-Xavier Gros, Laurence de Leval, Audrey Gros, and Marie Parrens
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Pathology and Forensic Medicine - Published
- 2023
8. Single-cell trajectories in Sézary syndrome
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Audrey Gros and Jean-Philippe Merlio
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medicine.anatomical_structure ,Immunology ,Cell ,medicine ,Cancer research ,Cell Biology ,Hematology ,Biology ,Biochemistry - Published
- 2021
9. L’analyse intégrative de lymphomes cutanés à grandes cellules B-lymphocytaires montre l’importance du profilage transcriptomique pour déterminer la cellule d’origine
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Audrey Gros, Sarah Menguy, Victor Bobée, Océane Ducharme, Béatrice Vergier, Marie Parrens, Marie Beylot-Barry, Anne Pham-Ledard, Philippe Ruminy, Fabrice Jardin, and Jean-Philippe Merlio
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Anatomy - Published
- 2022
10. PTEN alterations in sporadic and BRCA1-associated triple negative breast carcinomas
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Natalie Jones, Audrey Gros, Valérie Velasco, Valérie Dapremont, Véronique Brouste, Bernadette Gastaldello, Marc Debled, Christine Tunon de Lara, Françoise Bonnet, Emmanuelle Barouk-Simonet, Virginie Bubien, Laurence Venat, Gaëtan MacGrogan, Michel Longy, and Nicolas Sevenet
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Cancer Research ,Phenotype ,BRCA1 Protein ,Mutation ,Genetics ,PTEN Phosphohydrolase ,Humans ,Breast Neoplasms ,Female ,Triple Negative Breast Neoplasms ,RNA, Messenger ,Molecular Biology - Abstract
The similarities between sporadic basal-like breast cancer (BLBC) and BRCA1-mutated breast tumours raise the possibility that deregulation of the same pathway may underlie these tumour types. The aim of this study was to determine if PTEN aberrations are characteristic of both BRCA1 tumours and sporadic TN breast carcinomas with low BRCA1 expression, and can thus be used to identify sporadic tumours potentially sensitive to PARP inhibitors. Twelve BRCA1 tumours, 19 non-BRCA familial breast tumours and 71 unselected TN breast carcinomas were screened for PTEN mutations and assessed for PTEN expression and BRCA1 mRNA expression. Loss of PTEN expression was observed in 67% of BRCA1 tumours and more specifically in 89% of TN BRCA1 tumours highlighting the link between PTEN loss and BLBC in the context of germline BRCA1 mutations. Regarding unselected TN tumours, 56% showed PTEN expression loss and 35% displayed low BRCA1 mRNA expression. Unlike familial breast cancers with low BRCA1 mRNA expression, no significant correlation was observed between the loss of PTEN expression and low BRCA1 mRNA expression in this unselected TN tumours panel. Our data suggest that, unlike the germinal context, PTEN and BRCA1 alterations in sporadic TN breast tumours are independent events.
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- 2021
11. Intravascular large B-cell lymphoma involving pleural solitary fibrous tumor: A case report and literature review
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Samuel, Amintas, primary, Elodie, Laurent, additional, Audrey, Gros, additional, Come, Sesboue, additional, Jean-Philippe, Merlio, additional, and Marie, Parrens, additional
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- 2021
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12. L’expression intense de PD1 est associée au diagnostic de Sézary : étude chez 91 patients érythrodermiques
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Sarah Menguy, Jean-Philippe Vial, Brigitte Milpied, Marie Beylot-Barry, Camille Luherne, Thomas Ferte, Julien Seneschal, Audrey Gros, Béatrice Vergier, Anne Pham-Ledard, and Samuel Amintas
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Ocean Engineering ,Safety, Risk, Reliability and Quality - Published
- 2021
13. Deciphering discrepancies in cutaneous lymphomas genetics
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B. Vergier, M. Parrens, Marion Marty, Jean-Philippe Merlio, Audrey Gros, Anne Pham-Ledard, Marie Beylot-Barry, Martina Carlotti, and Sarah Menguy
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Oncology ,Cancer Research ,medicine.medical_specialty ,Mycosis fungoides ,business.industry ,Germinal center ,CBCL ,medicine.disease ,Lymphoma ,Clinical trial ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Mantle cell lymphoma ,business ,Pathological ,Anaplastic large-cell lymphoma - Abstract
In several instances, our group has reported opposite findings to others when analyzing the genetic features of primary cutaneous T-cell or B-cell lymphomas (CTCL or CBCL). This was especially the case for the absence of NAV3 rearrangements in CTCL, the low rate of BCL2 or MYC rearrangement in primary cutaneous follicle center lymphomas (CFCL) or primary cutaneous large B-cell lymphomas, leg-type (CLBCL, LT), respectively. Here, we review bias accounting for such discrepancies. Primary cutaneous lymphoma usually present with characteristic clinical and pathological features which serve as universal criteria for initial diagnosis and treatment. When required, extensive staging including CT scan, blood analysis and for some groups bone marrow staging, is mandatory to eliminate a secondary CTCL or CBCL. Early spreading may change the initial diagnosis and a long-term follow-up is also necessary to determine the risk for extracutaneous involvement. Non-uniform inclusion criteria and follow-up time may contribute to discrepancies, especially for studies claiming for a high rate of BCL2 rearrangement in CBCL. Most CBCL or CTCL usually display an indolent course except for aggressive subtypes arising de novo such as Sezary syndrome (SS), tumor or transformed mycosis fungoides (T-MF) or CLBCL-LT. Borderline cases between indolent and aggressive cutaneous lymphomas exist and may be called for example as leukemic CTCL or CBCL, not-otherwise specified (NOS) leading to heterogeneous terminology between centers. Moreover, aggressive CL are rare occurring mainly in adults or elderly that limits therapeutic options and comparison of small groups in retrospective series. The distribution of diagnosis between the three main primary CBCL including marginal-zone lymphoma (MZL), CFCL and CLBCL, LT has considerably evolved and its heterogeneity between centers may also hamper uniform findings. Our proposal to classify large CBCL according to germinal center or non-germinal center origin has so far not been validated by others while in systemic lymphomas genomic profiling appears mandatory to identify patients with impaired prognosis. In the most frequent cutaneous lymphomas, no highly recurrent genetic mutation is commonly used for diagnosis purpose. Some genetic lesion such as CCND1 rearrangement in mantle cell lymphoma can serve a positive criteria of secondary skin involvement. Alternatively, exceptional primary anaplastic large cell lymphoma (ALCL) bear ALK rearrangement preventing to use such criteria as a hallmark of secondary skin ALCL. BCL2 rearrangement in primary CFCL contributes to identify patients at risk for extracutaneous spreading. Most reports found negative data for NAV3 rearrangement in CTCL that may not be a primary oncogenic driver but a secondary event. Interestingly, MYC rearrangement or double-hits may have a low impact on prognosis in CBCL while they are usually associated with impaired prognosis in systemic or nodal lymphomas. Alternatively, some highly recurrent mutation such as those of MYD88 in CLBCL, LT should be routinely assessed. While clinical presentation will remain a basis for CL diagnosis and treatment, it is now time to integrate molecular profiling in research studies or clinical trials to standardize diagnosis and to identify patients which will exhibit therapeutic resistance to conventional first-line treatment.
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- 2021
14. Classification of primary cutaneous large B-cell lymphomas according to cell of origin is clinically relevant
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Béatrice Vergier, Fabrice Jardin, Jean-Philippe Merlio, Isabelle Cirilo Cassaigne, Marie Parrens, Victor Bobée, Audrey Gros, Anne Pham-Ledard, Marie Beylot-Barry, Océane Ducharme, Philippe Ruminy, and Sarah Menguy
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Cancer Research ,Pathology ,medicine.medical_specialty ,medicine.anatomical_structure ,Primary (chemistry) ,Oncology ,Cell of origin ,medicine ,Biology ,B cell - Published
- 2021
15. High PD1 expression H score is associated with Sézary diagnosis: study of 91 patients with erythroderma
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Béatrice Vergier, Julien Seneschal, Jean-Philippe Vial, Sarah Menguy, Audrey Gros, Anne Pham-Ledard, Marie Beylot-Barry, Camille Luherne, Brigitte Milpied, Samuel Amintas, and Thomas Ferte
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Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,Internal medicine ,medicine ,Erythroderma ,business ,Diagnosis Study ,medicine.disease ,Gastroenterology - Published
- 2021
16. Primary cutaneous follicle center lymphoma with Hodgkin and Reed-Sternberg-like cells: a new histopathologic variant
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Marie, Dilly, Houda, Ben-Rejeb, Béatrice, Vergier, Matthieu, Feldis, Louis, Toty, Olivier, Nohra, Marie, Beylot-Barry, Audrey, Gros, Jean-Philippe, Merlio, and Marie, Parrens
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- 2014
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17. Double-hit or dual expression of MYC and BCL2 in primary cutaneous large B-cell lymphomas
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Laurence Verneuil, Stéphane Dalle, Jean-Philippe Merlio, Serge Boulinguez, Sarah Menguy, Audrey Gros, Marie Beylot-Barry, Eric Frison, Anne Pham-Ledard, Olivier Dereure, Béatrice Vergier, Caroline Ram-Wolff, Laurent Machet, Sophie Dalac, Martina Prochazkova-Carlotti, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), CHU Toulouse [Toulouse], Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)
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Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Skin Neoplasms ,Dual expression ,Pathology and Forensic Medicine ,Proto-Oncogene Proteins c-myc ,03 medical and health sciences ,0302 clinical medicine ,Dermis ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Humans ,B cell ,Aged ,Aged, 80 and over ,Gene Rearrangement ,business.industry ,Large cell ,Gene rearrangement ,Middle Aged ,medicine.disease ,BCL6 ,3. Good health ,Lymphoma ,030104 developmental biology ,medicine.anatomical_structure ,Proto-Oncogene Proteins c-bcl-2 ,030220 oncology & carcinogenesis ,Female ,Lymphoma, Large B-Cell, Diffuse ,Differential diagnosis ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; In nodal diffuse large B-cell lymphoma, the search for double-hit with MYC and BCL2 and/or BCL6 rearrangements or for dual expression of BCL2 and MYC defines subgroups of patients with altered prognosis that has not been evaluated in primary cutaneous large B-cell lymphoma. Our objectives were to assess the double-hit and dual expressor status in a cohort of 44 patients with primary cutaneous large B-cell lymphoma according to the histological subtype and to evaluate their prognosis relevance. The 44 cases defined by the presence of more than 80% of large B-cells in the dermis corresponded to 21 primary cutaneous follicle centre lymphoma with large cell morphology and 23 primary cutaneous diffuse large B-cell lymphoma, leg type. Thirty-one cases (70%) expressed BCL2 and 29 (66%) expressed MYC. Dual expressor profile was observed in 25 cases (57%) of either subtypes (n = 6 or n = 19, respectively). Only one primary cutaneous follicle centre lymphoma, large-cell case had a double-hit status (2%). Specific survival was significantly worse in primary cutaneous diffuse large B-cell lymphoma, leg type than in primary cutaneous follicle centre lymphoma, large cell (p = 0.021) and for the dual expressor primary cutaneous large B-cell lymphoma group (p = 0.030). Both overall survival and specific survival were worse for patients belonging to the dual expressor primary cutaneous diffuse large B-cell lymphoma, leg type subgroup (p = 0.001 and p = 0.046, respectively). Expression of either MYC and/or BCL2 negatively impacted overall survival (p = 0.017 and p = 0.018 respectively). As the differential diagnosis between primary cutaneous follicle centre lymphoma, large cell and primary cutaneous diffuse large B-cell lymphoma, leg type has a major impact on prognosis, dual-expression of BCL2 and MYC may represent a new diagnostic criterion for primary cutaneous diffuse large B-cell lymphoma, leg type subtype and further identifies patients with impaired survival. Finally, the double-hit assessment does not appear clinically relevant in primary cutaneous large B-cell lymphoma.
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- 2018
18. Challenges in Assessing MYC Rearrangement in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg-Type
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Audrey Gros, Anne Pham-Ledard, Jean-Philippe Merlio, Marie Parrens, Marie Beylot-Barry, Béatrice Vergier, Elodie Laharanne, Martina Prochazkova-Carlotti, and Sarah Menguy
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Male ,Skin Neoplasms ,Genes, myc ,In situ hybridization ,Leg type ,Biology ,Pathology and Forensic Medicine ,Primary Cutaneous Diffuse Large B-Cell Lymphoma ,medicine ,Biomarkers, Tumor ,Humans ,Gene ,In Situ Hybridization, Fluorescence ,Aged ,Aged, 80 and over ,Gene Rearrangement ,Gene rearrangement ,Middle Aged ,medicine.disease ,Prognosis ,Lymphoma ,Cancer research ,Surgery ,Female ,Lymphoma, Large B-Cell, Diffuse ,Anatomy - Published
- 2019
19. Xenograft and cell culture models of Sézary syndrome reveal cell of origin diversity and subclonal heterogeneity
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Marie Beylot-Barry, Audrey Gros, Sandrine Poglio, Anne Pham-Ledard, Elodie Laharanne, Jean-Philippe Merlio, Martina Prochazkova-Carlotti, and Floriane Cherrier
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Adult ,Cancer Research ,Skin Neoplasms ,Cell of origin ,Cell Culture Techniques ,Apoptosis ,Mice, SCID ,Biology ,Article ,Mice ,Mice, Inbred NOD ,Genotype ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Sezary Syndrome ,Cancer models ,Cancer genetics ,Sezary Cell ,Cell Proliferation ,T-cell receptor ,Gene rearrangement ,Prognosis ,medicine.disease ,Xenograft Model Antitumor Assays ,Phenotype ,Clone Cells ,Lymphoma ,Genes, T-Cell Receptor ,Oncology ,Cell culture ,Cancer research - Abstract
Sézary Syndrome (SS) is a rare aggressive epidermotropic cutaneous T-cell lymphoma (CTCL) defined by erythroderma, pruritis, and a circulating atypical CD4 + T-cell clonal population. The diversity of Sézary cell (SC) phenotype and genotype may reflect either plasticity or heterogeneity, which was difficult to evaluate dynamically until the achievement of long-term SC expansion. Therefore, we developed six defined culture conditions allowing for the expansion of SC defined by their phenotype and monoclonality in four of seven SS cases. Engraftment of SC through the intrafemoral route into immunodeficient NOD.Cg-Prkdc(scid)Il2rg(tm1Wjll)/SzJ (NSG) mice was achieved in 2 of 14 SS cases. Secondary xenograft by percutaneous injection mimicked most of the features of SS with dermal infiltration, epidermotropism, and blood spreading. These models also allowed assessing the intra-individual heterogeneity of patient SC. Subclones sharing the same TCR gene rearrangement evolved independently according to culture conditions and/or after xenografting. This clonal selection was associated with some immunophenotypic plasticity and limited genomic evolution both in vitro and in vivo. The long-term amplification of SC allowed us to develop eight new SC lines derived from four different patients. These lines represent the cell of origin diversity of SC and provide new tools to evaluate their functional hallmarks and response to therapy.
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- 2021
20. Les mutations de la voie du BCR sont associées à la chimioresistance dans les lymphomes B cutanés de type jambe
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Océane Ducharme, Elodie Bohers, Nicolas Faur, Anne Pham-Ledard, B. Vergier, Fabrice Jardin, Marie Beylot-Barry, Pierre-Julien Viailly, Thomas Bandres, Audrey Gros, Jean-Philippe Merlio, and Eric Frison
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Anatomy - Abstract
Le lymphome cutane primitif B diffus a grandes cellules type jambe (LBC-TJ), le plus agressif des lymphomes B cutanes, presente des caracteristiques proches des lymphomes B diffus a grandes cellules (LBDGC) de type « Activated B- Cell-like » (ABC) avec une activation constitutive de la voie NF-κB (nuclear factor-kappa B). Initialement, notre equipe a demontre la haute prevalence de la mutation MYD88L265P dans les LBC-TJ, puis associee a l’equipe du Pr Jardin (INSERM UMR1245, Rouen), nous avons confirme par exome sequencing la tres haute prevalence des mutations MYD88, PIM1 et CD79B [1] . La prise en charge de ces patients demeure un enjeu therapeutique malgre l’amelioration de la survie a 5 ans de 38 % a 74 % par l’association du Rituximab (anti-CD20) avec une polychimiotherapie adaptee a l’âge mais environ 50 % de non reponse sont observees sans facteur predictif connu. Nous souhaitons identifier un profil moleculaire predictif de reponse therapeutique permettant une meilleure prise en charge de ces patients. Nous avons analyse 14 patients repondeurs et 18 non repondeurs a la R-polychimiotherapie par NGS via un panel de 36 genes importants dans la lymphomagenese. Pour 14 patients, nous avons egalement analyse la biopsie a la progression/rechute afin d’identifier les alterations genetiques selectionnees lors de l’echappement therapeutique. Les patients presentant une mutation de la voie du BCR (CD79A/B ou CARD11) ont une survie sans progression et une survie specifique diminuee (p = 0,002 et p = 0,03 respectivement) [2] . L’analyse des echantillons au diagnostic et a la rechute montre que les mutations des genes MYD88 et CD79B sont les plus conservees et que la frequence allelique de ces mutations est superieure a la progression/rechute. La caracterisation d’une mutation dans la voie du BCR chez les patients atteints d’un LBTJ laisse presager une resistance a la polychimiotherapie conventionnelle. Ces patients pourraient beneficier d’un traitement adjuvant ou d’une seconde ligne d’emblee afin d’ameliorer leur prise en charge.
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- 2021
21. Real Time Pathological and Molecular Characterization of Aggressive B-Cell Lymphomas Based on a National Network. a Lysa Project
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Christiane Copie Bergman, Elodie Bohers, Peggy Dartigues-Cuillères, Pierre-Julien Viailly, Philippe Ruminy, Vinciane Marchand, Marie-Helene Delfau-Larue, Corinne Haioun, Cyrielle Robe, Elsa Poullot, Steven Le Gouill, Yannick Le Bris, Céline Bossard, Anne Moreau, Vincent Ribrag, Valérie Camara-clayette, Cyril Quivoron, Gilles Salles, Sophie Cotteret, Pierre Sujobert, Alexandra Traverse-Glehen, Claire Mauduit, Pascaline Etancelin, Sarah Huet, Liana Veresezan, Krimo Bouabdallah, Marie Parrens, Audrey Gros, Samuel Amintas, David Sibon, Ludovic Lhermitte, Thomas Steimle, Sophie Kaltenbach, Bettina Fabiani, Camille Laurent, Barbara Burroni, Laurent Martin, Thierry Jo Molina, Lysa LYSARC study group, and Fabrice Jardin
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education.field_of_study ,medicine.medical_specialty ,Study phase ,Second line treatment ,Immunology ,Population ,Clinical course ,Cell Biology ,Hematology ,Biochemistry ,Who recommendations ,Molecular level ,Family medicine ,medicine ,Current employment ,education ,Who classification - Abstract
Introduction Aggressive B-cell lymphomas are heterogeneous in their clinical course and biological characteristics. They include diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS), high grade-B-cell lymphoma with double/triple-hit or NOS (HGBL), primary mediastinal B-cell lymphoma (PMBL). In order to better differentiate these entities, the WHO classification recommends using immunohistochemistry (IHC), FISH, targeted sequencing and gene expression profiles (GEP). However, these techniques are most often performed retrospectively in clinical trials, which is not representative of real life. In order to use these information to improve the current standard of treatment with targeted therapies adapted to lymphoma biology, we have set up a national network on behalf of the LYSA called RT3 (for Real-time tailored therapy) to demonstrate that we are able to comprehensively characterize aggressive B cell lymphomas in a clinically relevant timeline. Materials and methods Patients > 18 years of age with untreated aggressive B-cell lymphoma were included prospectively from 21 LYSA centers. FFPE specimens were analyzed and classified according to WHO classification, benefiting from an IHC profile (Hans algorithm, BCL2, MYC), FISH analysis (BCL6, BCL2, MYC break apart and MYC-IGH/IGL/IGK fusion probes), targeted NGS analysis and a targeted GEP using RT-MLPA (Bobée et al. J Mol diagn 2017). A first part of the study phase was carried out in an oligocentric manner with only 2 referral platforms for pathological analysis and molecular characterization. The second phase was the implementation of 7 RT3 platforms spread over France. The main objective was to evaluate the capacity of the network to provide an exhaustive histopathological and molecular characterization 4 days before theoretical R-CHOP21 C3 administration (within 38 days after D1 cycle 1). Results The oligocentric cohort 1 prospectively included 72 patients in 6 months: 19 had insufficient material or inappropriate diagnosis to be qualified and 53 benefited from the complete analysis on referral platforms. A complete characterization 4 days before RCHOP-C3 was provided to the clinician in 47 cases (88.7%), allowing to further implement the network with 7 platforms and 23 clinical investigation centers. 183 patients were included in the second phase in 9 months, 35 were excluded for inadequate diagnosis/material. On this population, 143 (96.6%) complete patient-reports were provided with a median time of 32 days (1-50). Finally, 201 cases were retained in the Full Analysis Set for which tumor samples fulfilled all prerequisites and diagnosis of DLBCL was confirmed by RT3 platforms. The clinical characteristics were as follows: median age of 61 y (20-92), with 45.2% of pts with aaIPI 2-3and 67.1% with Ann Arbor stage III-IV; 1L treatment consisted mainly of RCHOP (RCHOP14/21 = 136, 72.3%). 7% of patients were treated with experimental drugs. 76% presented with extranodal involvement. After pathological review, 139 (69%) patients were classified as DLBCL-NOS (41% GCB; 58% nGCB), 11 (5%) as HGBL-NOS, 8 (4%) as HGBL-DH and 18 (9%) as PMBL, 3 (1%) as EBV+ DLBCL-NOS, 9 (4%) as FL-3B, 7 (3%) transformed DLBCL, 2 (1%) plasmablastic, 1 (0.5%) unclassified, 1 (0.5%) DLBCL with IRF4 rearrangement. By immunohistochemistry, 22 cases were CD5+, 74% were BCL2+, and 53% MYC+ and 49% as double expressors. BCL2/18q21, BCL6/3q27 and MYC/8q24 breaks were observed in 14% (29/201), 25% (50/201) and 12% (25/201) of the cases respectively. MYC partner gene was available in 10/29 cases (5 MYC-IG, 5 non-IG). At the molecular level, PIM1 was the most frequently mutated gene in the entire cohort (36%). In the ABC subtype, MYD88 was mutated in 48% of cases. In the GCB cohort, SOCS1 was the most frequently mutated gene (30%). In the HGBL cohort, MYC was the most mutated gene (43%). Conclusion This study demonstrates that this RT3 LYSA network allowed a real time pathological and molecular characterization of aggressive B-cell lymphomas according to the WHO recommendations. The RT3 network provides relevant informations to the clinician before R-CHOP21 C3, that might contribute to modify the treatment eventually adding targeted therapies or tailor a second line treatment. This network should be used as a basis for future clinical trials. Inter platforms reproducibility and prognostic relevance of the RT3 project will be presented. Disclosures Haioun: Gilead: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Miltenyi: Honoraria; Servier: Honoraria; Roche: Honoraria; Celgene: Honoraria. Le Gouill:Roche Genentech, Janssen-Cilag and Abbvie, Celgene, Jazz pharmaceutical, Gilead-kite, Loxo, Daiichi-Sankyo and Servier: Honoraria; Loxo Oncology at Lilly: Consultancy. Ribrag:arGEN-X-BVBA: Research Funding; BAY1000394 studies on MCL: Patents & Royalties; Institut Gustave Roussy: Current Employment; argenX: Current equity holder in publicly-traded company, Research Funding; Epizyme: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Infinity: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses; Nanostring: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Honoraria; Pharmamar: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AZD: Honoraria, Other; Eisai: Honoraria; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees. Salles:Takeda: Honoraria; Karyopharm: Honoraria; Genmab: Honoraria, Other; Debiopharm: Consultancy, Honoraria, Other: consultancy or advisory role; Autolos: Other: consultancy or advisory role; Abbvie: Other: consultancy or advisory role; Roche: Honoraria, Other: consultancy or advisory role; Novartis: Honoraria, Other: consultancy or advisory role; MorphoSys: Honoraria, Other: consultancy or advisory role; Janssen: Honoraria, Other: consultancy or advisory role; Epizyme: Honoraria, Other: consultancy or advisory role; Kite, a Gilead Company: Honoraria, Other: consultancy or advisory role ; BMS/Celgene: Honoraria, Other: consultancy or advisory role. Sujobert:Sunesis: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead/Kyte: Membership on an entity's Board of Directors or advisory committees. Bouabdallah:Gilead Sciences: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Sibon:takeda france: Consultancy.
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- 2020
22. Assessment of BRAFV600E mutation in pulmonary Langerhans cell histiocytosis in tissue biopsies and bronchoalveolar lavages by droplet digital polymerase chain reaction
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Gaël Dournes, Marion Marty, Hugues Begueret, Camille Brochet, Elodie Blanchard, Jean-Philippe Merlio, Séverine Verdon, Charline Caumont, Thomas Bandres, Audrey Gros, and Clémence Pierry
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Biology ,medicine.disease_cause ,Pulmonary Langerhans cell histiocytosis ,Pathology and Forensic Medicine ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,medicine ,Digital polymerase chain reaction ,In patient ,Molecular Biology ,Polymerase chain reaction ,Mutation ,medicine.diagnostic_test ,Cell Biology ,General Medicine ,Molecular biology ,BRAF V600E ,030104 developmental biology ,Bronchoalveolar lavage ,030220 oncology & carcinogenesis ,Immunohistochemistry - Abstract
The neoplastic nature of pulmonary Langerhans cell histiocytosis (PLCH) is still debated. As the detection of BRAF V600E and MAP2K1 mutations in patients with PCLH is now considered for such assessment, the aim of our study was to evaluate digital droplet polymerase chain reaction (ddPCR) in PCLH diagnosis. We retrospectively analyzed BRAFV600E detection in a cohort of 42 PCLH tissues and 18 bronchoalveolar lavages (BALs) by ddPCR, immunohistochemistry, high-resolution melting PCR (HRM), and next-generation sequencing (NGS). The presence of BRAFV600E mutation was assessed by at least two concordant techniques to further evaluate specificity and sensitivity of each method. The BRAF V600E mutation prevalence was detected in 18 out of 41 cases by ddPCR, 10 out of 36 cases by HRM PCR, and 16 out of 31 cases by NGS. BRAFV600E immunohistochemistry sensitivity was 94%, and specificity was 79%. HRM PCR sensitivity was only 59%, and specificity was 100%. NGS sensitivity and specificity were 100% for interpretable cases (n = 31), but in 11 cases, this technique was non-contributive. The analysis of BAL samples by ddPCR revealed a BRAFV600E mutation both in tissue and in BAL samples in one patient, a wild-type status both in tissue and in BAL samples in two patients, and a wild-type BRAF status in BAL and a BRAFV600E mutation in tissue samples in four patients. The study supports the usefulness of ddPCR for BRAF status assessment in either tissue or BAL samples to increase the accuracy of PLCH diagnosis.
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- 2017
23. Mutations of the B-Cell Receptor Pathway Confer Chemoresistance in Primary Cutaneous Diffuse Large B-Cell Lymphoma Leg Type
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Thomas Bandres, Audrey Gros, Anne Pham-Ledard, Elodie Bohers, Pierre-Julien Viailly, Fabrice Jardin, Marie Beylot-Barry, Jean-Philippe Merlio, Béatrice Vergier, Eric Frison, Nicolas Faur, Océane Ducharme, CHU Bordeaux [Bordeaux], Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département de pathologie [Hôpital Haut Lévêque], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], and UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)
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0301 basic medicine ,Oncology ,Male ,Skin Neoplasms ,Biochemistry ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,ComputingMilieux_MISCELLANEOUS ,Aged, 80 and over ,Middle Aged ,Prognosis ,3. Good health ,Treatment Outcome ,030220 oncology & carcinogenesis ,Rituximab ,Female ,Lymphoma, Large B-Cell, Diffuse ,CD79 Antigens ,medicine.drug ,Signal Transduction ,medicine.medical_specialty ,B-cell receptor ,Receptors, Antigen, B-Cell ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Dermatology ,03 medical and health sciences ,Internal medicine ,medicine ,Primary Cutaneous Diffuse Large B-Cell Lymphoma ,Biomarkers, Tumor ,Humans ,Progression-free survival ,Molecular Biology ,Survival analysis ,Aged ,Biologic marker ,business.industry ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Extremities ,Cell Biology ,medicine.disease ,Survival Analysis ,Lymphoma ,CARD Signaling Adaptor Proteins ,030104 developmental biology ,Drug Resistance, Neoplasm ,Guanylate Cyclase ,Mutation ,business ,Diffuse large B-cell lymphoma - Abstract
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) preferentially involves the lower limb in elderly subjects. A combination of polychemotherapy and rituximab has improved prognosis. However, about 50% of patients will experience progression or relapse without any predictive biologic marker of therapeutic response. The mutational profile of PCLBCL-LT has highlighted mutations contributing to constitutive NF-κB and B-cell receptor (BCR) signaling pathways but has not demonstrated clinical utility. Therefore, the mutational status of 32 patients with PCLBCL-LT (14 patients with complete durable response and 18 patients with relapsing or refractory disease) was determined with a dedicated lymphopanel. Tumor pairs at diagnosis and relapse or progression were analyzed in 14 relapsing or refractory patients. Patients with PCLBCL-LT harboring one mutation that targets one of the BCR signaling genes, CD79A/B or CARD11, displayed a reduced progression-free survival and specific survival (median 18 months, P = 0.002 and 51 months, P = 0.03, respectively, whereas median duration in the wild-type group was not reached) and were associated with therapeutic resistance (P = 0.0006). Longitudinal analyses revealed that MYD88 and CD79B were the earliest and among the most mutated genes. Our data suggest that evaluating BCR mutations in patients with PCLBCL-LT may help to predict first-line therapeutic response and to select targeted therapies.
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- 2019
24. The Need for a Consensus Next-generation Sequencing Panel for Mature Lymphoid Malignancies
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Gilles Salles, Catherine Thieblemont, Vahid Asnafi, Yannick Le Bris, Elizabeth Macintyre, Audrey Gros, Pierre Sujobert, David Sibon, Sarah Huet, Cedric Pastoret, Jean-Philippe Merlio, Clémentine Sarkozy, Fabrice Jardin, Laurence de Leval, Claude Preudhomme, Frederic Davi, Philippe Gaulard, Mary Callanan, Jonchère, Laurent, Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Division de cardiologie [CHU Vaudois] (CHUV), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Paris Diderot - Paris 7 (UPD7), Université Paris Descartes - Paris 5 (UPD5), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, CHU Henri Mondor, Université Paris-Est Marne-la-Vallée (UPEM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor [Créteil], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille
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0303 health sciences ,lcsh:RC633-647.5 ,business.industry ,MEDLINE ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,lcsh:Diseases of the blood and blood-forming organs ,Computational biology ,Hematology ,DNA sequencing ,03 medical and health sciences ,Text mining ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,030220 oncology & carcinogenesis ,Perspective ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Medicine ,business ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,030215 immunology - Abstract
International audience; Supplemental Digital Content is available in the text.
- Published
- 2018
25. MYD88 Somatic Mutation Is a Diagnostic Criterion in Primary Cutaneous Large B-Cell Lymphoma
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Vanessa Szablewski, François Le Gall, Anne de Muret, Jean-Philippe Merlio, Nicolas Ortonne, Agnès Carlotti, Maxime Battistella, David Cappellen, Marie Beylot-Barry, Béatrice Vergier, Audrey Gros, F. Franck, François Comoz, Anne Pham-Ledard, Sarah Menguy, Anne Croue, Brigitte Balme, Marie-Hélène Lorton, Laurence Lamant, Physiopathologie du cancer du foie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cancer et Transplantation : Physiopathologie et Réponse Thérapeutique (UMR 1165), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM U955, équipe 9, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'Anatomie Pathologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'anatomie et cytologie pathologiques [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service de Pathologie, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Pontchaillou [Rennes], CHU Clermont-Ferrand, Département de Pathologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Département de biologie de la tumeur, CHU Bordeaux [Bordeaux], Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], and Jonchère, Laurent
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PCFCL ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Primary cutaneous B-cell lymphoma ,Dermatology ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,Biochemistry ,primary cutaneous follicle center lymphoma ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,medicine ,primary cutaneous B-cell lymphoma ,PCBCL ,B-cell lymphoma ,Molecular Biology ,ComputingMilieux_MISCELLANEOUS ,primary cutaneous marginal zone lymphoma ,GC ,business.industry ,Germinal center ,Cell Biology ,[SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology ,PCLBCL-LT ,medicine.disease ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,germinal center ,primary cutaneous large B-cell lymphoma-leg type ,030220 oncology & carcinogenesis ,PCMZL ,Immunology ,Mutation (genetic algorithm) ,Cancer research ,Myeloid Differentiation Factor 88 ,Primary cutaneous marginal zone lymphoma ,Differential diagnosis ,business ,[SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology - Abstract
International audience; no abstract
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- 2016
26. Challenging a dogma: co-mutations exist in MAPK pathway genes in colorectal cancer
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Isabelle Soubeyran, Audrey Gros, Florence Pedeutour, Jean-Philippe Merlio, Thomas Grellety, Valérie Duranton-Tanneur, and Antoine Italiano
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Adult ,Male ,Proto-Oncogene Proteins B-raf ,0301 basic medicine ,Neuroblastoma RAS viral oncogene homolog ,MAPK/ERK pathway ,Class I Phosphatidylinositol 3-Kinases ,MAP Kinase Signaling System ,Colorectal cancer ,Biology ,medicine.disease_cause ,GTP Phosphohydrolases ,Pathology and Forensic Medicine ,Proto-Oncogene Proteins p21(ras) ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,medicine ,Humans ,neoplasms ,Molecular Biology ,Aged ,Retrospective Studies ,Aged, 80 and over ,Sanger sequencing ,Mutation ,High-Throughput Nucleotide Sequencing ,Membrane Proteins ,Cancer ,Cell Biology ,General Medicine ,Middle Aged ,medicine.disease ,digestive system diseases ,030104 developmental biology ,030220 oncology & carcinogenesis ,symbols ,Cancer research ,Female ,KRAS ,Mitogen-Activated Protein Kinases ,Colorectal Neoplasms ,Carcinogenesis - Abstract
Sequencing of genes encoding mitogen-activated protein kinase (MAPK) pathway proteins in colorectal cancer (CRC) has established as dogma that of the genes in a pathway only a single one is ever mutated. We searched for cases with a mutation in more than one MAPK pathway gene (co-mutations). Tumor tissue samples of all patients presenting with CRC, and referred between 01/01/2008 and 01/06/2015 to three French cancer centers for determination of mutation status of RAS/RAF+/-PIK3CA, were retrospectively screened for co-mutations using Sanger sequencing or next-generation sequencing. We found that of 1791 colorectal patients with mutations in the MAPK pathway, 20 had a co-mutation, 8 of KRAS/NRAS, and some even with a third mutation. More than half of the mutations were in codons 12 and 13. We also found 3 cases with a co-mutation of NRAS/BRAF and 9 with a co-mutation of KRAS/BRAF. In 2 patients with a co-mutation of KRAS/NRAS, the co-mutation existed in the primary as well as in a metastasis, which suggests that co-mutations occur early during carcinogenesis and are maintained when a tumor disseminates. We conclude that co-mutations exist in the MAPK genes but with low frequency and as yet with unknown outcome implications.
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- 2016
27. Speed of leukemia development and genetic diversity in xenograft models of T cell acute lymphoblastic leukemia
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André Baruchel, Judith Landman-Parker, Daniel Lewandowski, Paola Ballerini, Jean Soulier, Thierry Leblanc, Sandrine Poglio, Audrey Gros, Elodie Laharanne, Julien Calvo, Françoise Pflumio, Aurélie Caye, and Emmanuelle Clappier
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0301 basic medicine ,Human leukemia ,Time Factors ,T cell ,Lymphoblastic Leukemia ,Transplantation, Heterologous ,Mice, Nude ,Antigens, CD34 ,Mice, Transgenic ,Mice, SCID ,Newly diagnosed ,Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ,clonal selection ,Genetic Heterogeneity ,Mice ,Young Adult ,03 medical and health sciences ,Mice, Inbred NOD ,hemic and lymphatic diseases ,Cell Line, Tumor ,medicine ,Animals ,Humans ,xenograft ,Child ,Translational oncology ,business.industry ,Genetic Variation ,leukemia initiating cells ,medicine.disease ,Molecular biology ,3. Good health ,Leukemia ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Immunology ,Disease Progression ,Heterografts ,Genetic selection ,CD34 ,T-ALL ,business ,Neoplasm Transplantation ,Research Paper - Abstract
// Sandrine Poglio 1, 2, 3, 4 , Daniel Lewandowski 2, 3, 4, 5 , Julien Calvo 1, 2, 3, 4 , Aurelie Caye 6, 7 , Audrey Gros 8, 9 , Elodie Laharanne 8, 9 , Thierry Leblanc 10 , Judith Landman-Parker 11 , Andre Baruchel 10 , Jean Soulier 6, 12, 13 , Paola Ballerini 1, 2, 3, 4, 11 , Emmanuelle Clappier 6, 12, 13 , Francoise Pflumio 1, 2, 3, 4 1 Commissariat a l’Energie Atomique et aux Energies Alternatives (CEA), DSV-IRCM-SCSR-LSHL, UMR 967, Fontenay-aux-Roses, France 2 INSERM, U967, Fontenay-aux-Roses, France 3 Universite Paris Diderot, Sorbonne Paris Cite, UMR 967, Fontenay-aux-Roses, France 4 Universite Paris-Sud, UMR 967, Fontenay-aux-Roses, France 5 CEA, DSV-IRCM-SCSR-LRTS, UMR 967, Fontenay-aux-Roses, France 6 Universite Paris Diderot, Paris, France 7 Assistance Publique-Hopitaux de Paris (AP-HP), Departement de Genetique, UF de Genetique Moleculaire, Hopital Robert Debre Paris, France 8 INSERM, UMR1053 Bordeaux Research in Translational Oncology (BaRITOn), Bordeaux, France 9 Universite de Bordeaux, Bordeaux, France 10 AP-HP, Service d’hematologie Pediatrique, Hopital Robert Debre, Paris, France 11 AP-HP, Service d’hematologie Pediatrique, Hopital Armand Trousseau, Paris, France 12 AP-HP, Laboratoire d’Hematologie, Hopital Saint-Louis, Paris, France 13 Team Genome and Cancer, U944 INSERM, Paris, France Correspondence to: Francoise Pflumio, email: francoise.pflumio@cea.fr Sandrine Poglio, email: sandrine.poglio@u-bordeaux.fr Keywords: T-ALL, leukemia initiating cells, clonal selection, CD34, xenograft Received: June 29, 2015 Accepted: April 22, 2016 Published: May 12, 2016 ABSTRACT T cell acute lymphoblastic leukemia (T-ALL) develops through accumulation of multiple genomic alterations within T-cell progenitors resulting in clonal heterogeneity among leukemic cells. Human T-ALL xeno-transplantation in immunodeficient mice is a gold standard approach to study leukemia biology and we recently uncovered that the leukemia development is more or less rapid depending on T-ALL sample. The resulting human leukemia may arise through genetic selection and we previously showed that human T-ALL development in immune-deficient mice is significantly enhanced upon CD7 + /CD34 + leukemic cell transplantations. Here we investigated the genetic characteristics of CD7 + /CD34 + and CD7 + /CD34 − cells from newly diagnosed human T-ALL and correlated it to the speed of leukemia development. We observed that CD7 + /CD34 + or CD7 + /CD34 − T-ALL cells that promote leukemia within a short-time period are genetically similar, as well as xenograft-derived leukemia resulting from both cell fractions. In the case of delayed T-ALL growth CD7 + /CD34 + or CD7 + /CD34 − cells were either genetically diverse, the resulting xenograft leukemia arising from different but branched subclones present in the original sample, or similar, indicating decreased fitness to mouse micro-environment. Altogether, our work provides new information relating the speed of leukemia development in xenografts to the genetic diversity of T-ALL cell compartments.
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- 2016
28. Primary digestive melanoma in association with tubular adenoma: a case report illustrating the distinction from metastatic colonic melanoma
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Caroline Dutriaux, Charline Caumont, Jean-Philippe Merlio, David Cappellen, Béatrice Vergier, Adeline Furudoï, Christine Merlio, J. F. Goussot, Audrey Gros, and Christophe Barberis
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Adenoma ,Male ,Pathology ,medicine.medical_specialty ,Colorectal cancer ,Comorbidity ,Pathology and Forensic Medicine ,Metastasis ,Neoplasms, Multiple Primary ,Lesion ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Tubular adenoma ,medicine ,Humans ,Melanoma ,Aged ,Lamina propria ,business.industry ,Mucosal melanoma ,Neoplasms, Second Primary ,medicine.disease ,medicine.anatomical_structure ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,medicine.symptom ,business - Abstract
We report here an exceptional pattern of atypical lentiginous melanocytic proliferation within an adenoma, leading to focal lamina propria infiltration and pulmonary metastasis, which was considered as primary colonic mucosal melanoma (MM) in a Caucasian patient. Such case illustrates the diagnosis criteria required to differentiate primary MM from colonic metastasis of melanoma, including the absence of past history of other primary melanoma, a unique colonic and abdominal lesion with predominant features of in situ lentiginous MM and a very focal and unique invasive area without other digestive tract or abdominal localization. This tumor displayed a KIT exon 11 mutation leading to a unique combination of p.I571M and p.D572G deleterious amino acid changes. Such pattern also favors the diagnosis as KIT appears as a master oncogenic player in MM oncogenesis.
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- 2016
29. A Single-Arm Phase II Trial of Lenalidomide in Relapsing or Refractory Primary Cutaneous Large B-Cell Lymphoma, Leg Type
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Reda Bouabdallah, Laurent Mortier, Stéphane Dalle, Pascal Joly, Eve Maubec, Martine Bagot, N. Bonnet, Saskia Ingen-Housz-Oro, Stéphane Barete, Béatrice Vergier, Gaëlle Quéreux, Jean-Philippe Merlio, Anne-Bénédicte Duval-Modeste, D. Mermin, Marie Beylot-Barry, Aline Maillard, Florent Grange, Pierre-Julien Vially, Eric Frison, Caroline Ram-Wolff, Audrey Gros, Anne Pham-Ledard, Isabelle Templier, CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Unité de Soutien Méthodologique à la Recherche Clinique (USMR), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service de dermatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Universitaire de Lille (CHU de Lille), CHU Henri Mondor, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de référence des mastocytoses (CEREMAST), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de Dermatologie [CHU de Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Laboratoire d'Histologie et de Pathologie moléculaire des tumeurs, Université Bordeaux Segalen - Bordeaux 2-EA 2406, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de référence des mastocytoses, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Male ,medicine.medical_specialty ,Skin Neoplasms ,Biopsy ,[SDV]Life Sciences [q-bio] ,Dermatology ,Biochemistry ,Gastroenterology ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Immunologic Factors ,Progression-free survival ,B-cell lymphoma ,Molecular Biology ,Lenalidomide ,ComputingMilieux_MISCELLANEOUS ,Aged ,Skin ,Aged, 80 and over ,Leg ,Dose-Response Relationship, Drug ,business.industry ,Remission Induction ,Cell Biology ,medicine.disease ,3. Good health ,Lymphoma ,Survival Rate ,030104 developmental biology ,Treatment Outcome ,030220 oncology & carcinogenesis ,Rituximab ,Female ,France ,Lymphoma, Large B-Cell, Diffuse ,Neoplasm Recurrence, Local ,business ,Diffuse large B-cell lymphoma ,[SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology ,medicine.drug - Abstract
Although the combination of rituximab and polychemotherapy has improved prognosis of primary cutaneous diffuse large B-cell lymphoma, leg type, the advanced age of patients limits therapeutic options in relapsing/refractory cases. A multicenter, single-arm, phase II trial was conducted to assess the benefits and safety of lenalidomide in refractory/relapsing primary cutaneous diffuse large B-cell lymphoma, leg type. The primary endpoint was the 6-month overall response rate. Secondary endpoints were 12-month overall response rate, overall and specific survival, duration of response, progression-free survival, safety, and identification of prognostic factors. Among the 19 patients included, the 6-month overall response rate was 26.3% (90% confidence interval [CI] = 11–47.6), including four complete responses and one partial response. At 12 months, there were still two complete responses and one partial response. Median progression-free survival was 4 months. Median overall and specific survivals were 19.4 and 23.8 months, respectively. Reduced doses tended to be associated with higher 6-month overall response rate and progression-free survival. Absence of the MYD88L265P mutation was associated with a higher overall response under treatment (80.0% vs. 33.3%; P = 0.05). The most common grade 3 adverse events were hematologic. Two grade 5 adverse events occurred (sepsis and pulmonary embolism). Lenalidomide at reduced doses may allow prolonged responses in a few patients and represents a therapeutic option in relapsing/refractory primary cutaneous diffuse large B-cell lymphoma, leg type.
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- 2018
30. Word-final fortis / lenis contrast in English plosives: lists of words in isolation read aloud by French-speaking learners
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Nadine Herry-Benit, Takeki Kamiyama, Ioana Trifu-Dejeu, Audrey Gros-Bonfiglioli, Linguistique Empirique : Cognition, Société et Langage (LECSeL), Transferts critiques anglophones (TransCrit), Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris 8 Vincennes-Saint-Denis (UP8), LPP - Laboratoire de Phonétique et Phonologie - UMR 7018 (LPP), Université Sorbonne Nouvelle - Paris 3-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches Anglophones (CREA (EA 370)), Université Paris Nanterre (UPN), and Kamiyama, Takeki
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fortis / lenis contrast ,Philosophy ,plosive ,duration ,[SHS.LANGUE] Humanities and Social Sciences/Linguistics ,French-speaking learner ,anglais ,durée ,opposition fortis / lenis ,English ,occlusive ,production ,[SHS.LANGUE]Humanities and Social Sciences/Linguistics ,apprenant francophone ,Humanities - Abstract
Word-final fortis / lenis contrast in English plosives: lists of words in isolation read aloud by French-speaking learners The acquisition of the word-initial fortis / lenis contrast in English by speakers of other languages has been investigated by many researchers, but empirical studies on this contrast in word-final position seems to have been conducted less extensively, and especially on speakers of languages in which word-final voicing distinction is known to be absent or neutralized (Smith et al., 2009 ; Skarnitzl & Šturm, 2016). In this study, 6 French-speaking learners of English, who have voicing contrast word-finally in their first language, pronounced 30 words each in isolation. It was observed that the previous vowel, which is described as a primary cue in native speakers' speech, was significantly shorter before fortis than lenis (Wilcoxon rank sum test) in 5 learners out of 6, but some learners also showed cases of different voicing patterns for lenis than native speakers (voiced release for lenis; end of voicing earlier than natives)., L'opposition fortis / lenis en début de mot en anglais acquise par des locuteurs d'autres langues a été étudiée par de nombreux chercheurs, mais la position finale de mot semble avoir été moins abordée dans des études empiriques et ceux qui existent portent surtout sur les locuteurs de langues caractérisées par une absence ou neutralisation de cette opposition en fin de mot (Smith et al., 2009 ; Skarnitzl & Šturm, 2016). Dans cette étude, 6 apprenantes francophones de l'anglais, qui connaissent une opposition de voisement en fin de mot dans leur première langue, ont prononcé 30 mots isolés. Il a été observé que la voyelle précédente, considérée comme indice primaire chez les anglophones natifs, était significativement plus courte devant les fortis que lenis (test de la somme des rangs de Wilcoxon) par 5 apprenantes sur 6, mais certaines d'entre elles ont montré des réalisations phonétiques de voisement différentes des natifs (relâchement voisé pour lenis; fin de voisement plus tôt que les natifs).
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- 2018
31. Clinical, histological and molecular predictors of metastatic melanoma responses to anti-PD-1 immunotherapy
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Béatrice Vergier, Sorilla Prey, Nicolas Meyer, Frantz Dupuis, Thomas Filleron, Léonor Chaltiel, Caroline Dutriaux, Laurence Lamant, Audrey Gros, Marie Beylot-Barry, Marie-Laure Jullie, Emilie Gérard, and Nouritza Torossian
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Oncology ,Neuroblastoma RAS viral oncogene homolog ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,Antigens, Differentiation, Myelomonocytic ,Receptors, Cell Surface ,B7-H1 Antigen ,Article ,GTP Phosphohydrolases ,03 medical and health sciences ,0302 clinical medicine ,Antigens, CD ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,030212 general & internal medicine ,Progression-free survival ,Neoplasm Metastasis ,Melanoma ,Aged ,Retrospective Studies ,business.industry ,Membrane Proteins ,Retrospective cohort study ,Histiocytes ,Neoplasms, Second Primary ,Immunotherapy ,Middle Aged ,medicine.disease ,Progression-Free Survival ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,Mutation ,Biomarker (medicine) ,Immunohistochemistry ,Female ,business ,Progressive disease - Abstract
Background Prescribing anti-programmed death-1 (PD-1) immunotherapy for advanced melanoma is currently not restricted by any biomarker assessment. Determination of programmed death-ligand-1 (PD-L1)-expression status is technically challenging and is not mandatory, because negative tumours also achieve therapeutic responses. However, reproducible biomarkers predictive of a response to anti-PD-1 therapy could contribute to improving therapeutic decision-making. Methods This retrospective study on 70 metastatic melanoma patients was undertaken to evaluate the relationships between clinical, histological, immunohistochemical and/or molecular criteria, and the 6-month objective response rate. Results Better objective response rates were associated with metachronous metastases (P = 0.04), PD-L1 tumour- and/or immune-cell status (P = 0.01), CD163+ histiocytes at advancing edges (P = 0.009) of primary melanomas and NRAS mutation (P = 0.019). Moreover, CD163+ histiocytes at advancing edges (P = 0.04) were associated with longer progression-free survival (PFS), and metachronous metastases with longer overall survival (P = 0.02) and PFS (P = 0.049). Conclusions Combining these reproducible biomarkers could help improve therapeutic decision-making for patients with progressive disease.
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- 2018
32. Definition of a minimal genes set for mature lymphoid blood diseases
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Yannick Le Bris, Claude Preudhomme, Elizabeth Macintyre, Pierre Sujobert, Mary Callanan, Frederic Davi, Sarah Huet, Gilles Salles, Clémentine Sarkozy, Cedric Pastoret, Laurence de Leval, Fabrice Jardin, Audrey Gros, Catherine Thieblemont, Philippe Gaulard, David Sibon, Vahid Asnafi, Jean-Philippe Merlio, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Métabolisme et physiologie rénale (CRC - UMR_S 1138), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École Pratique des Hautes Études (EPHE), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), CHU Henri Mondor [Créteil], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine
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Set (abstract data type) ,0303 health sciences ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Hematology ,Computational biology ,Biology ,Gene ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology - Abstract
National audience
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- 2018
33. Évaluation des critères cliniques, pathologiques et moléculaires prédictifs de réponse à l’immunothérapie anti-PD1 dans le mélanome métastatique : analyse rétrospective de 70 patients
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E. Gérard, B. Vergier, N. Torossian, S. Prey, Marie Beylot-Barry, Laurence Lamant, Nicolas Meyer, L. Chaltiel, Thomas Filleron, C. Dutriaux, Audrey Gros, F. Dupuis, and Marie-Laure Jullie
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Dermatology - Abstract
Introduction La positivite du marqueur PD-L1 dans le melanome non resecable ou metastatique n’est pas obligatoire pour initier une immunotherapie. L’utilisation du statut PD-L1 est discutee car certains patients avec une tumeur PD-L1 negative ont des durees de reponse prolongee sous immunotherapie. De plus, les methodes de determination du statut PD-L1 sont tres heterogenes et les seuils de positivite different dans les etudes. L’objectif principal etait d’evaluer la correlation entre des criteres cliniques, histologiques, moleculaire et la reponse objective aux anti-PD1. Patients et methodes Etude retrospective bicentrique incluant tous les patients dont les prelevements de tumeurs primitives et metastatiques fixees et incluses en paraffine etaient disponibles avant la premiere injection d’immunotherapie. Les donnees demographiques, histologiques (statut PD-L1 tumoral et lymphocytaire, expression du CD163+), moleculaire (mutation BRAF, NRAS et cKIT), la tolerance et l’efficacite du traitement a 6 mois (taux de reponse objective, survie globale et survie sans progression) ont ete recueillies. Le seuil de positivite PD-L1 retenu etait de 5 % sur les cellules tumorales. Resultats La presence de metastases metachrones (p = 0,04), une positivite de PD-L1 de plus de 5 % de la surface tumorale globale (cellules tumorales et/ou immunes, p = 0,01), la presence de plus de 10 % d’histiocytes CD163+ au front d’invasion (p = 0,009), et le statut NRAS mute (p = 0,019) dans les melanomes primitifs etaient correles a un meilleur taux de reponse objective a 6 mois. De plus la presence de metastases metachrones etait associee a une meilleure survie globale et survie sans progression. Plus de 10 % d’histiocytes CD163+ au front d’invasion (p = 0,04) etait associe a une survie sans progression augmentee. Discussion Le PD-L1 est exprime sur les histiocytes en contact etroit avec les melanocytes de la tumeur. L’evaluation conjointe de ce statut sur les cellules tumorales et sur les cellules immunes est plus fiable que sur la tumeur seule. A notre connaissance, l’expression du CD163+ sur le front d’invasion de la tumeur n’a jamais ete evaluee dans le melanome et pourrait etre un biomarqueur utile. Conclusion Le statut PD-L1 seul ne peut pas etre utilise comme biomarqueur de la reponse therapeutique aux anti-PD1, mais doit s’interpreter avec d’autres criteres comme la presence de metastases synchrones, la presence de plus de 10 % d’histiocytes CD163+ au front d’invasion ou le statut de NRAS.
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- 2018
34. Identification de marqueurs de réponse au rituximab-polychimiothérapie des lymphomes B cutanés primitifs diffus à grandes cellules de type jambe par analyse protéomique et mutationnelle
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Marie Beylot-Barry, Audrey Gros, Anne Pham-Ledard, J.-P. Merlio, Béatrice Vergier, Elodie Laharanne, Océane Ducharme, Martina Prochazkova-Carlotti, and N. Faur
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Dermatology - Abstract
Introduction Le lymphome B cutane primitif diffus a grandes cellules de type jambe (LBCGC-MI) survient chez les sujets âges. Le traitement standard associant le rituximab et une polychimiotherapie adaptee a l’âge (R-PCT) a ameliore la survie a 5 ans de 41 a 73 %. Cependant, les non-reponses primaires et surtout secondaires (recidives) restent frequentes (40 %) et sont un veritable enjeu, en l’absence de critere clinicobiologique predictif. Notre equipe a contribue a l’identification d’alterations genetiques frequentes de la voie NF-κB et du « B-Cell Receptor » ou BCR. Notre objectif etait d’identifier des marqueurs predictifs de reponse a la R-PCT par analyse mutationnelle et proteique. Patients et methodes Etude retrospective multicentrique 1 d’une cohorte de patients traites par R-PCT (13 bons repondeurs BR et 19 non repondeurs NR) pour un LBCGC-MI, par sequencage nouvelle generation (NGS) cible sur 36 genes importants pour la lymphomagenese et par analyse proteomique realises sur des biopsies tumorales fixees par le formol (32 biopsies au diagnostic, 13 biopsies a la recidive). Resultats Le NGS realise sur 32 patients au diagnostic montrait des mutations de plusieurs genes ciblant la voie NF-κB comme PIM1 (72 %), MYD88 (69 %) et des mutations ciblant celle du BCR comme CD79B (53 %). La non-reponse a la R-PCT etait fortement correlee a la presence d’une mutation pour un des 3 genes de la voie du BCR, CARD11, CD79A ou B (p = 0,001). La non-reponse etait egalement associee aux mutations ciblant uniquement le BCR (CD79A ou B) (p = 0,01) et a une plus courte survie sans progression (mediane de 18 mois vs 45 mois, p = 0,02). L’etude proteomique comparative de 12 NR et 12 BR au diagnostic montrait une expression differentielle de plusieurs marqueurs dont une proteine de la voie du BCR permettant d’identifier les BR (sensibilite : 83 %, specificite : 92 %). L’analyse comparee du profil mutationnel de 13 patients a la recidive et au diagnostic mettait en evidence une selection de clones avec un enrichissement de mutations de genes « drivers » et de clones exempts d’autres mutations identifiees au diagnostic. Discussion Les mutations de la voie du BCR semblent etre associees au risque de recidive. Ceci pourrait justifier l’utilisation d’inhibiteurs de kinase du BCR, comme l’ibrutinib qui a montre des resultats encourageants dans les lymphomes B systemiques ganglionnaire diffus a grandes cellules de type « ABC » sauf en cas de mutation CARD11 car en aval de la cible de l’ibrutinib. Les variations du nombre de copies des genes permettraient une meilleure comprehension de l’evolution clonale entre tumeur au diagnostic et a la recidive. Conclusion Cette etude souligne la place centrale de l’activation chronique du BCR dans la reponse au traitement des patients atteints de LBCGC-MI, traites par R-PCT.
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- 2018
35. Impact des profils « double-hit » et « double expression » de BCL2 et MYC dans les lymphomes B à grandes cellules primitifs cutanés
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Caroline Ram-Wolff, Eric Frison, S. Dalle, Groupe français d’étude des lymphomes cutanés, J.-P. Merlio, Laurent Machet, Sophie Dalac, Sarah Menguy, Marie Beylot-Barry, Serge Boulinguez, Martina Prochazkova-Carlotti, Olivier Dereure, Audrey Gros, L. Verneuil, Anne Pham-Ledard, and B. Vergier
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Dermatology - Abstract
Introduction Au sein des lymphomes B diffus a grandes cellules ganglionnaires, la presence d’un « double-hit » (rearrangements de 2 oncogenes MYC et BCL2 et/ou BCL6) ainsi que la double expression de BCL2 et MYC definissent des sous-groupes de patients ayant un pronostic defavorable. La valeur clinique de ces profils n’a pas ete etudiee dans les lymphomes B a grandes cellules primitifs cutanes (LBGCC). Materiel et methodes Il s’agit d’une etude multicentrique, incluant retrospectivement des cas de LBGCC (> 80 % de grandes cellules), diagnostiques selon les criteres de la classification OMS 2017. Nous avons recherche des rearrangements de MYC, BCL2 et BCL6 par hybridation in situ en fluorescence et le statut « double expression » (> 50 % et > 40 % de cellules tumorales exprimant BCL2 et MYC) par immunohistochimie. Les resultats ont ete correles avec les donnees cliniques (recidive, survie) et une analyse statistique a la recherche de valeur diagnostique et pronostique a ete realisee. Resultats Quarante-quatre LBGCC etaient inclus : 21 lymphomes B cutanes centro-folliculaires a grandes cellules (LBCF-GC) et 23 lymphomes B diffus a grandes cellules, de type jambe (LBTJ). Deux cas (5 %) presentaient un rearrangement de MYC : 1 LBTJ ( Fig. 1A ) et 1 LBCF-GC. Un rearrangement de BCL6 etait observe dans 5 cas (12 %) : 4 cas de LBTJ et 1 cas de LBCF-GC ( Fig. 1B ). Aucun rearrangement de BCL2 n’a ete observe. Seul un cas (2 %), correspondant a un LBCF-GC, avait un statut double-hit (rearrangement de MYC et BCL6), sans lien apparent avec le pronostic (remission complete apres 29 mois de suivi). Comme attendu, les LBTJ avaient une survie globale et specifique inferieure aux LBCF-GC (respectivement p = 0,001 et p = 0,021). Trente et un cas (70 %) exprimaient BCL2 et 29 (66 %) exprimaient MYC. Un profil double expression etait present dans 25 cas (57 %) : 6 cas de LBCF-GC et 19 cas de LBTJ. Le profil double expression etait plus souvent associe au sous-type histologique LBTJ (p = 0,006) et associe a un mauvais pronostic (survie globale inferieure, p = 0,002). De plus, au sein du groupe des LBTJ, la presence d’un profil double expression impactait negativement la survie (p = 0,001) ( Fig. 2 ). Discussion Certains cas de LBGCC restent difficiles a classer selon les criteres morphologiques et phenotypiques habituellement utilises. Le profil double expression de MYC et BCL2 est associe a une survie inferieure et pourrait representer un critere diagnostique aidant a differencier les LBCF-GC des LBTJ, deux entites au pronostic et a la prise en charge therapeutique differents. Conclusion Contrairement au lymphome B diffus a grandes cellules ganglionnaires, la recherche du statut double-hit ne semble pas pertinente dans les LBGCC. Le profil double expression peut apporter une aide diagnostique parmi les LBGCC et permet d’identifier un sous-groupe de patients ayant une survie inferieure au sein des LBTJ.
- Published
- 2018
36. PLCG1 Gene Mutations Are Uncommon in Cutaneous T-Cell Lymphomas
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Elodie Laharanne, Charline Caumont, David Cappellen, Martina Prochazkova-Carlotti, Audrey Gros, Anne Pham-Ledard, Cécile Boucher, Pierre Mélard, Béatrice Vergier, Jean-Philippe Merlio, Marie Beylot-Barry, and Edith Chevret
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Pathology ,medicine.medical_specialty ,Skin Neoplasms ,T cell ,DNA Mutational Analysis ,Dermatology ,Sensitivity and Specificity ,Biochemistry ,Sampling Studies ,High Resolution Melt ,PLCG1 Gene ,Humans ,Medicine ,Lymphomatoid papulosis ,PLCG1 ,Molecular Biology ,Phospholipase C gamma ,business.industry ,Biopsy, Needle ,Cutaneous T-cell lymphoma ,Cell Biology ,medicine.disease ,Lymphoma, T-Cell, Cutaneous ,medicine.anatomical_structure ,Mutation ,Cancer research ,business - Published
- 2015
37. Clinical and genomic analysis of a randomised phase II study evaluating anastrozole and fulvestrant in postmenopausal patients treated for large operable or locally advanced hormone-receptor-positive breast cancer
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Marc Debled, Hayssam Soueidan, L. Mauriac, Thomas Bachelot, Justine Rudewicz, Barbara Lortal, Pamela Rabbitts, Hervé Bonnefoi, Richard Iggo, Catherine Daly, Gaëtan MacGrogan, Henry M. Wood, N. Madranges, C. Breton-Callu, Christine Tunon de Lara, Macha Nikolski, N Quenel-Tueux, Audrey Gros, Marina Pulido, M. Fournier, Florence Dalenc, Service d'Oncologie Médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Validation et identification de nouvelles cibles en oncologie (VINCO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2, Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Centre de Bioinformatique de Bordeaux (CBIB), CGFB, Unité de recherche clinique et épidémiologique, Centre d'investigation clinique - épidémiologie clinique, Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme de génétique moléculaire des cancers d'Aquitaine, Centre de Physiopathologie de Toulouse-Purpan (INSERM U563 - CNRS UMR1037), Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut Claudius Regaud, Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Médecine Nucléaire, Centre Léon Bérard [Lyon], Service de Chirurgie, Biothérapies des maladies génétiques et cancers, and Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Oncology ,Cancer Research ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,anastrozole ,Anastrozole ,Phases of clinical research ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Breast Neoplasms ,hormone-receptor-positive cancer ,Palpation ,law.invention ,large operable or locally advanced breast cancer ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Randomized controlled trial ,law ,Internal medicine ,Nitriles ,medicine ,Humans ,Aged ,030304 developmental biology ,Aged, 80 and over ,Gynecology ,0303 health sciences ,Estradiol ,fulvestrant ,medicine.diagnostic_test ,Fulvestrant ,business.industry ,Middle Aged ,Triazoles ,medicine.disease ,3. Good health ,Postmenopause ,Clinical trial ,neo-adjuvant ,030220 oncology & carcinogenesis ,Toxicity ,Clinical Study ,endocrine treatment ,Female ,business ,medicine.drug - Abstract
International audience; BACKGROUND:The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment.METHODS:One hundred and twenty post-menopausal patients were randomised to receive 1 mg anastrozole (61 patients) or 500 mg fulvestrant (59 patients) for 6 months. Genomic DNA copy number profiles were generated for a subgroup of 20 patients before and after treatment.RESULTS:A total of 108 patients were evaluable for efficacy and 118 for toxicity. The objective response rate determined by clinical palpation was 58.9% (95% CI=45.0-71.9) in the anastrozole arm and 53.8% (95% CI=39.5-67.8) in the fulvestrant arm. The breast-conserving surgery rate was 58.9% (95% CI=45.0-71.9) in the anastrozole arm and 50.0% (95% CI=35.8-64.2) in the fulvestrant arm. Pathological responses >50% occurred in 24 patients (42.9%) in the anastrozole arm and 13 (25.0%) in the fulvestrant arm. The Ki-67 score fell after treatment but there was no significant difference between the reduction in the two arms (anastrozole 16.7% (95% CI=13.3-21.0) before, 3.2% (95% CI=1.9-5.5) after, n=43; fulvestrant 17.1% (95%CI=13.1-22.5) before, 3.2% (95% CI=1.8-5.7) after, n=38) or between the reduction in Ki-67 in clinical responders and non-responders. Genomic analysis appeared to show a reduction of clonal diversity following treatment with selection of some clones with simpler copy number profiles.CONCLUSIONS:Both anastrozole and fulvestrant were effective and well-tolerated, enabling breast-conserving surgery in over 50% of patients. Clonal changes consistent with clonal selection by the treatment were seen in a subgroup of patients.British Journal of Cancer advance online publication 14 July 2015; doi:10.1038/bjc.2015.247 www.bjcancer.com.
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- 2015
38. Remarkable Response to Crizotinib in Woman With Anaplastic Lymphoma Kinase–Rearranged Anaplastic Thyroid Carcinoma
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Isabelle Soubeyran, Audrey Gros, Antoine Italiano, Camille Dupin, Isabelle Hostein, Bénédicte Henriques de Figueiredo, Gaëlle Pérot, Françoise Bonichon, Yann Godbert, Frédéric Chibon, Genevieve Belleannée, and Agnès Daubech
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Cancer Research ,Lung Neoplasms ,Time Factors ,Pyridines ,Biopsy ,medicine.medical_treatment ,Antineoplastic Agents ,Thyroid Carcinoma, Anaplastic ,Anaplastic thyroid carcinoma ,Thyroid carcinoma ,Crizotinib ,Predictive Value of Tests ,Biomarkers, Tumor ,medicine ,Humans ,Anaplastic lymphoma kinase ,Anaplastic Lymphoma Kinase ,Thyroid Neoplasms ,Precision Medicine ,Protein Kinase Inhibitors ,In Situ Hybridization, Fluorescence ,Aged ,Neoplasm Staging ,Gene Rearrangement ,Chemotherapy ,business.industry ,Remission Induction ,Thyroidectomy ,Receptor Protein-Tyrosine Kinases ,Gene rearrangement ,Immunohistochemistry ,Treatment Outcome ,Oncology ,Chemotherapy, Adjuvant ,Cancer research ,Pyrazoles ,Female ,Tomography, X-Ray Computed ,business ,medicine.drug - Published
- 2015
39. Assessment of BRAF
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Clémence, Pierry, Charline, Caumont, Elodie, Blanchard, Camille, Brochet, Gael, Dournes, Audrey, Gros, Thomas, Bandres, Séverine, Verdon, Marion, Marty, Hugues, Bégueret, and Jean-Philippe, Merlio
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Adult ,Genetic Markers ,Male ,Proto-Oncogene Proteins B-raf ,Biopsy ,DNA Mutational Analysis ,High-Throughput Nucleotide Sequencing ,Middle Aged ,Bronchoalveolar Lavage ,Immunohistochemistry ,Polymerase Chain Reaction ,Sensitivity and Specificity ,Histiocytosis, Langerhans-Cell ,Mutation ,Humans ,Female ,Bronchoalveolar Lavage Fluid ,Lung ,Retrospective Studies - Abstract
The neoplastic nature of pulmonary Langerhans cell histiocytosis (PLCH) is still debated. As the detection of BRAF
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- 2017
40. TP53 alterations in primary and secondary Sézary syndrome: A diagnostic tool for the assessment of malignancy in patients with erythroderma
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Elodie Laharanne, Sandrine Poglio, Edith Chevret, Sabine Berhouet, Jean-Philippe Vial, Thomas Bandres, Audrey Gros, B. Vergier, Jean-Philippe Merlio, Marie Vergier, Anne Pham-Ledard, Marie Beylot-Barry, and Martina Prochazkova-Carlotti
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Male ,0301 basic medicine ,Pathology ,Skin Neoplasms ,endocrine system diseases ,Physiology ,Gene Identification and Analysis ,Erythroderma ,lcsh:Medicine ,Pathology and Laboratory Medicine ,Cohort Studies ,White Blood Cells ,Animal Cells ,Polymorphism (computer science) ,Medicine and Health Sciences ,Medicine ,Stage (cooking) ,Frameshift Mutation ,lcsh:Science ,Immune Response ,In Situ Hybridization, Fluorescence ,Aged, 80 and over ,Multidisciplinary ,Fluorescent in Situ Hybridization ,T Cells ,Middle Aged ,Flow Cytometry ,Body Fluids ,Blood ,Female ,Anatomy ,Cellular Types ,Dermatitis, Exfoliative ,Research Article ,medicine.medical_specialty ,DNA Copy Number Variations ,Immune Cells ,Immunology ,Molecular Probe Techniques ,Research and Analysis Methods ,Malignancy ,Polymorphism, Single Nucleotide ,Peripheral blood mononuclear cell ,Frameshift mutation ,03 medical and health sciences ,Signs and Symptoms ,stomatognathic system ,Diagnostic Medicine ,Genetics ,Point Mutation ,Humans ,Sezary Syndrome ,Molecular Biology Techniques ,Mutation Detection ,Molecular Biology ,neoplasms ,Aged ,Inflammation ,Mycosis fungoides ,Blood Cells ,business.industry ,Point mutation ,lcsh:R ,Biology and Life Sciences ,Human Genetics ,Cell Biology ,Genes, p53 ,medicine.disease ,Probe Hybridization ,030104 developmental biology ,Mutation ,lcsh:Q ,business ,Cytogenetic Techniques - Abstract
Recent massive parallel sequencing data have evidenced the genetic diversity and complexity of Sézary syndrome mutational landscape with TP53 alterations being the most prevalent genetic abnormality. We analyzed a cohort of 35 patients with SS and a control group of 8 patients with chronic inflammatory dermatoses. TP53 status was analyzed at different clinical stages especially in 9 patients with a past-history of mycosis fungoides (MF), coined secondary SS. TP53 mutations were only detected in 10 patients with either primary or secondary SS (29%) corresponding to point mutations, small insertions and deletions which were unique in each case. Interestingly, TP53 mutations were both detected in sequential unselected blood mononuclear cells and in skin specimens. Cytogenetic analysis of blood specimens of 32 patients with SS showed a TP53 deletion in 27 cases (84%). Altogether 29 out of 35 cases exhibited TP53 mutation and/or deletion (83%). No difference in prognosis was observed according to TP53 status while patients with secondary SS had a worse prognosis than patients with primary SS. Interestingly, patients with TP53 alterations displayed a younger age and the presence of TP53 alteration at initial diagnosis stage supports a pivotal oncogenic role for TP53 mutation in SS as well as in erythrodermic MF making TP53 assessment an ancillary method for the diagnosis of patients with erythroderma as patients with inflammatory dermatoses did not display TP53 alteration.
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- 2017
41. Primary cutaneous follicle center lymphoma with Hodgkin and Reed-Sternberg-like cells: a new histopathologic variant
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Matthieu Feldis, Audrey Gros, Marie Dilly, Louis Toty, Olivier Nohra, Marie Parrens, Jean-Philippe Merlio, Béatrice Vergier, Marie Beylot-Barry, and Houda Ben-Rejeb
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education.field_of_study ,Pathology ,medicine.medical_specialty ,Histology ,CD30 ,Follicular dendritic cells ,medicine.diagnostic_test ,Population ,Follicular lymphoma ,Dermatology ,CD15 ,Biology ,medicine.disease ,BCL6 ,Pathology and Forensic Medicine ,Lymphoma ,immune system diseases ,hemic and lymphatic diseases ,medicine ,education ,Fluorescence in situ hybridization - Abstract
Primary cutaneous follicle center lymphoma (PCFCL) is the most frequent cutaneous B-cell lymphoma. A 62-year-old man presented with a solitary indolent subcutaneous nodule for 3 years duration, without other abnormalities. Histological examination showed lymphoproliferation with a nodular growth pattern characterized by fibrous collagen bands surrounding nodules. The nodules were composed of medium-sized centrocytes admixed with many large multilobulated and lacunar cells without eosinophils or granulomatous aspect. Hodgkin-like cells were CD30+, CD15+, PAX5+, OCT2+, BOB1+, MUM1+, Ki67+, Bcl6+ and focally CD20+ and EMA-, CD79a-, Bcl2- and CD10-. The medium-sized cells were CD20+, CD79a+, Bcl2+, Bcl6+ and CD10+, enmeshed in a network of CD21-positive follicular dendritic cells. Epstein-Barr virus detection was negative. Interphase fluorescence in situ hybridization showed the absence of BCL2 or BCL6 rearrangement. In such a case, the presence of Hodgkin-like cells intermixed with the tumor population may result in a pitfall diagnosis of classical Hodgkin lymphoma (CHL). Differential diagnoses to be ruled out are secondary or primary skin localization of rather CHL, or systemic follicular lymphoma. Several clinical, radiological, histological, immunohistochemical and molecular arguments indicated the diagnosis of PCFCL. To our knowledge, this is the first report of PCFCL with Hodgkin-like cells.
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- 2014
42. Parallel FISH and Immunohistochemical Studies of ALK Status in 3244 Non–Small-Cell Lung Cancers Reveal Major Discordances
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Audrey Gros, Julien Dagher, Laura Mesturoux, Gwendoline Soler, Dominique Dachary, Jean-Philippe Merlio, Leila Dufrenot, Dan Cristian Chiforeanu, Marc-Antoine Belaud-Rotureau, Véronique Catros, Hugues Begueret, Alexandra Lespagnol, Michele Le Calve, Vincent Jauffret, F Dugay, Florian Cabillic, Romain Corre, Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Registre Multicentrique à Vocation Nationale des Mésothéliomes Pleuraux (MESONAT), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Service de pneumologie [Rennes] = Pneumology [Rennes], Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Molecular Engines Laboratories, Université Paris Descartes - Paris 5 (UPD5), INSERM EMI0210 (EMI0210), Institut National de la Santé et de la Recherche Médicale (INSERM), Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire d'Histologie et de Pathologie moléculaire des tumeurs, Université Bordeaux Segalen - Bordeaux 2-EA 2406, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre national référent cancers rares - mésothéliomes malins pleuraux et tumeurs péritonéales rares ( MESOPATH ), CHU Caen-Hôpital côte de nacre, Service d'anatomie et cytologie pathologiques [Rennes], Service de pneumologie, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Laboratoire de Biologie et de Pharmacologie Appliquée ( LBPA ), École normale supérieure - Cachan ( ENS Cachan ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), INSERM EMI0210 ( EMI0210 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
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Oncology ,Male ,Pathology ,Lung Neoplasms ,Cohort Studies ,Immunoenzyme Techniques ,Anaplastic lymphoma kinase ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,hemic and lymphatic diseases ,Medicine ,In Situ Hybridization, Fluorescence ,Aged, 80 and over ,Gene Rearrangement ,0303 health sciences ,Middle Aged ,Prognosis ,Immunohistochemistry ,3. Good health ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Biomarker (medicine) ,Female ,medicine.drug ,Adult ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.drug_class ,Adenocarcinoma ,Fluorescent in situ hybridization ,03 medical and health sciences ,Carcinoma, Adenosquamous ,Young Adult ,Internal medicine ,Carcinoma ,Biomarkers, Tumor ,Humans ,030304 developmental biology ,Aged ,Neoplasm Staging ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Crizotinib ,business.industry ,Non–small-cell lung cancer ,Receptor Protein-Tyrosine Kinases ,Gene rearrangement ,Biomarker ,medicine.disease ,ALK inhibitor ,Clinical trial ,business ,[ SDV.GEN ] Life Sciences [q-bio]/Genetics ,Non-small-cell lung cancer ,Follow-Up Studies - Abstract
International audience; Introduction: Anaplastic lymphoma kinase (ALK) rearrangements occur in 1% to 7% of non-small-cell lung cancers (NSCLCs). Crizotinib, an ALK inhibitor, has been demonstrated to provide dramatic clinical benefits in ALK-positive advanced-stage NSCLC. Fluorescent in situ hybridization (FISH) has been established in clinical trials as the standard procedure method for detecting ALK rearrangements. Although the detection of ALK by immunohistochemistry (IHC) has been proposed for the screening of patients, large-scale studies are warranted to validate such a hierarchical approach. Methods: In this article, we report the largest series thus far of parallel FISH and IHC ALK testing in 3244 consecutive NSCLC cases analyzed at two independent French centers. Results: FISH-positive and/or IHC-positive results were demonstrated in 150 of 3244 cases (4.6%). An imbalanced sex ratio was detected, with women exhibiting a 2.2-fold relative risk for an alteration. Strikingly, only 80 of 150 specimens were classified as ALK positive by both techniques. The specimens with discordant FISH/IHC analyses were FISH-positive/IHC-negative (36), FISH-negative/IHC-positive (19), or FISH-noncontributive/IHC-positive (15). Thus, a single FISH or IHC analysis performed alone would have failed to detect approximately one-fourth of the ALK-positive cases with similar findings in our two centers. Conclusions: This study highlights the feasibility of systematic NSCLC testing by both FISH and IHC in routine practice. Many preanalytical factors may account for the apparent discrepancies between both methods, suggesting that hierarchical screening may underscore ALK-positive cases. This significant level of discrepancy supports the need of combined testing to optimize the detection of ALK-inhibitor-eligible patients given that some patients with discordant testing were found to respond to crizotinib.
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- 2014
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43. Hybridization Capture-Based Next-Generation Sequencing to Evaluate Coding Sequence and Deep Intronic Mutations in the NF1 Gene
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Thomas Bandres, Audrey Gros, Nathalia S. Oliveira, Rodrigo Soares de Moura Neto, Mauro Geller, Karin Soares Gonçalves Cunha, Yamina Idrissi, Carolina Cruz de Souza, David Cappellen, Rosane Silva, Anna Karoline Fausto, and Jean-Philippe Merlio
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0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,Neurofibromatosis 1 ,lcsh:QH426-470 ,Pseudogene ,030105 genetics & heredity ,Biology ,DNA sequencing ,Article ,Frameshift mutation ,03 medical and health sciences ,symbols.namesake ,Exon ,NF1 gene ,next generation sequencing ,Genetics ,Gene ,Genetics (clinical) ,Sanger sequencing ,eye diseases ,nervous system diseases ,lcsh:Genetics ,030104 developmental biology ,RNA splicing ,symbols ,Human genome - Abstract
Neurofibromatosis 1 (NF1) is one of the most common genetic disorders and is caused by mutations in the NF1 gene. NF1 gene mutational analysis presents a considerable challenge because of its large size, existence of highly homologous pseudogenes located throughout the human genome, absence of mutational hotspots, and diversity of mutations types, including deep intronic splicing mutations. We aimed to evaluate the use of hybridization capture-based next-generation sequencing to screen coding and noncoding NF1 regions. Hybridization capture-based next-generation sequencing, with genomic DNA as starting material, was used to sequence the whole NF1 gene (exons and introns) from 11 unrelated individuals and 1 relative, who all had NF1. All of them met the NF1 clinical diagnostic criteria. We showed a mutation detection rate of 91% (10 out of 11). We identified eight recurrent and two novel mutations, which were all confirmed by Sanger methodology. In the Sanger sequencing confirmation, we also included another three relatives with NF1. Splicing alterations accounted for 50% of the mutations. One of them was caused by a deep intronic mutation (c.1260 + 1604A > G). Frameshift truncation and missense mutations corresponded to 30% and 20% of the pathogenic variants, respectively. In conclusion, we show the use of a simple and fast approach to screen, at once, the entire NF1 gene (exons and introns) for different types of pathogenic variations, including the deep intronic splicing mutations.
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- 2016
44. Double-hit and dual expression of MYC and BCL2 in primary cutaneous large B-cell lymphomas
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Caroline Ram-Wolff, Laurent Machet, Martina Prochazkova-Carlotti, Serge Boulinguez, Stéphane Dalle, Olivier Dereure, Sophie Dalac, Laurence Verneuil, Jean-Philippe Merlio, Sarah Menguy, Marie Beylot-Barry, Béatrice Vergier, Audrey Gros, Anne Pham-Ledard, and Eric Frison
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Cancer Research ,Double hit ,Primary (chemistry) ,medicine.anatomical_structure ,Oncology ,medicine ,Cancer research ,Biology ,Dual expression ,B cell - Published
- 2019
45. Spleen Histologic Appearance in Common Variable Immunodeficiency: Analysis of 17 Cases
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Marie Parrens, Enio Furudoï, Audrey Gros, Jean-François Viallard, Adeline Furudoï, Sophie Stanislas, Mohamed Hamidou, Eric Oksenhendler, and Jean-Philippe Merlio
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0301 basic medicine ,Adult ,Male ,Pathology ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Splenectomy ,Spleen ,Pathology and Forensic Medicine ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Medicine ,Humans ,Child ,Aged ,Autoimmune disease ,Granuloma ,biology ,business.industry ,Common variable immunodeficiency ,Hyperplasia ,Middle Aged ,medicine.disease ,Marginal zone ,Immunohistochemistry ,030104 developmental biology ,medicine.anatomical_structure ,Common Variable Immunodeficiency ,Child, Preschool ,biology.protein ,Surgery ,Female ,Anatomy ,Antibody ,business ,Immunoglobulin Heavy Chains ,030215 immunology - Abstract
Histologic and phenotypic analyses of splenectomy samples from 17 patients with common variable immunodeficiency (CVID) showed the following nonspecific, evocative, white-pulp lesions: white-pulp hyperplasia (WPH) with reactive follicles, giant follicles (GFs), marginal zone hyperplasia, periarteriolar T-zone hyperplasia (PATH) and/or granulomas, which enabled us to discern 2 groups: the first (n=6) composed of WPH with reactive follicles without granulomas, and the second (n=9) characterized by the presence of granulomas with or without WPH. All specimens were Epstein-Barr virus negative by in situ hybridization. Molecular analyses revealed a polyclonal immunoglobulin heavy chain gene (IGH) rearrangement (n=12). WPH-only patients were mostly female individuals and younger at CVID onset, diagnosis, and splenectomy, but their interval between the first symptom and diagnosis was longer; they had more associated infectious events, autoimmune disease, pulmonary complications, and liver regenerative nodular hyperplasia; their IgG, IgA, and IgM concentrations were also higher. Granuloma-group patients were mostly male individuals; were older at CVID onset, diagnosis, and splenectomy; had disseminated granulomatous disease, but infectious events, autoimmune disease, pulmonary complications, and liver regenerative nodular hyperplasia were less common; their immunoglobulin concentrations were lower. Histologic comparisons between the WPH-only and granuloma groups showed more intense WPH and more intense marginal zone hyperplasia and fewer GFs in the former versus more developed PATH and more common GFs in the latter. The results of this novel comparative study of the histologic patterns of 17 CVID patients' evocative splenic lesions suggested different biological and clinical profiles.
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- 2016
46. La cellule de Sézary : une nouvelle définition phénotypique et moléculaire
- Author
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Thomas Bandres, Audrey Gros, Jean-Philippe Merlio, Béatrice Vergier, Anne Pham-Ledard, Marie Vergier, Marie Beylot-Barry, Jean-Philippe Vial, Sandrine Poglio, Martina Prochazkova-Carlotti, Sabine Berhouet, Elodie Laharanne, and Edith Chevret
- Subjects
0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,Anatomy - Abstract
De recentes analyses de sequencage massif [1] , [2] ont permis de mettre en evidence la diversite et la complexite du profil mutationnel du syndrome de Sezary (SS). Ces differentes etudes ont cependant definit l’alteration de TP53 comme anomalie la plus frequente. Dans ce contexte, nous avons analyse le statut TP53 dans une cohorte de 35 patients SS ainsi qu’un groupe temoin compose de 8 patients presentant une dermatose inflammatoire chronique. Le statut TP53 a ete analyse a differents stades cliniques, notamment pour 9 patients appeles « SS secondaire » car ayant developpe un syndrome de Sezary apres un mycosis fongoides (MF). Une mutation du gene TP53 de type mutation ponctuelle ou petite insertion/deletion a ete caracterisee chez 10 (29 %) patients SS d’emblee ou secondaire. Aucune mutation n’est commune a plusieurs patients. A noter que ces mutations sont presentes a la fois dans les cellules mononuclees du sang et dans les echantillons de peau. Des analyses cytogenetiques realisees en parallele sur les cellules mononuclees du sang de 32 patients ont rapporte 27 (84 %) cas de deletion. Au total, une mutation et/ou une deletion de TP53 a ete caracterisee sur 29 (83 %) des 35 cas testes. Aucune difference de pronostique n’a ete observee selon le statut TP53 mais les patients presentant un SS secondaire ont un pronostic plus sombre que les patients presentant un SS d’emblee. Il est interessant de souligner que la presence de l’alteration de TP53 au diagnostic de SS (ou de MF s’il s’agit d’un SS secondaire) supporte l’hypothese que la mutation de TP53 jouerait un role pivot dans l’oncogenese du SS et du MF, et que l’etude du statut de TP53 et notamment l’absence d’alteration de TP53 pourrait etre utile au diagnostic differentiel des patients atteints de dermatoses inflammatoires.
- Published
- 2017
47. French multicentric validation of ALK rearrangement diagnostic in 547 lung adenocarcinomas
- Author
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Anne McLeer-Florin, Isabelle Rouquette, Nolwenn Le Stang, Jean-Michel Vignaud, Audrey Mansuet-Lupo, Mojgan Devouassoux-Shisheboran, Françoise Thivolet, Stéphane Garcia, Valerie Grégoire, Martine Antoine, Frédérique Penault-Llorca, Sylvie Lantuejoul, Marius Ilie, Paul Hofman, Françoise Galateau-Sallé, Nathalie Monhoven, Hélène Blons, Audrey Gros, Hugues Begueret, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Cancers et préventions, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Hôpital Pasteur [Nice] (CHU), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire d'anatomie pathologique - [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Service de Pathologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Anatomo-Pathologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Anatomie et cytologie pathologique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Service d’Anatomie et de Cytologie Pathologiques [Louis Pradel - CHU Lyon], Hôpital Louis Pradel [CHU - HCL], Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Centre Jean Perrin, CRLCC Jean Perrin, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hospices Civils de Lyon (HCL), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Hôpital Nord [CHU - APHM]-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
- Subjects
Pulmonary and Respiratory Medicine ,Adult ,Male ,Identification ,EML4/ALK Fusion Gene ,Lung Neoplasms ,Inhibitor ,Adolescent ,Pyridines ,[SDV]Life Sciences [q-bio] ,Quantitative Reverse Transcriptase PCR ,Adenocarcinoma of Lung ,Biology ,Adenocarcinoma ,Recommendations ,Sensitivity and Specificity ,Association ,Young Adult ,Crizotinib ,EML4-Alk Fusion Gene ,hemic and lymphatic diseases ,medicine ,TaqMan ,Anaplastic lymphoma kinase ,Humans ,Anaplastic Lymphoma Kinase ,Kinase activity ,False Negative Reactions ,In Situ Hybridization, Fluorescence ,Features ,Aged ,Cancer ,Aged, 80 and over ,Gene Rearrangement ,Reverse Transcriptase Polymerase Chain Reaction ,Receptor Protein-Tyrosine Kinases ,In-Situ Hybridization ,Middle Aged ,medicine.disease ,Molecular biology ,Immunohistochemistry ,3. Good health ,Pyrazoles ,Female ,France ,medicine.drug - Abstract
Anaplastic lymphoma kinase (ALK) gene rearrangements in lung adenocarcinoma result in kinase activity targetable by crizotinib. Although fluorescence in situ hybridisation (FISH) is the reference diagnostic technique, immunohistochemistry (IHC) could be useful for pre-screening.Diagnostic yields of ALK IHC, FISH and quantitative reverse transcriptase PCR performed in 14 French pathology/molecular genetics platforms were compared. 547 lung adenocarcinoma specimens were analysed using 5A4 and D5F3 antibodies, two break-apart FISH probes and TaqMan kits. Clinicopathological data were recorded.140 tumours were ALK rearranged (FISH with ≥15% of rearranged cells) and 400 were ALK FISH negative (ALK patients were young (p=0.003), mostly females (p=0.007) and light/nonsmokers (p20%. Variants were undetected in 36% of ALK tumours.Discordances predominated with FISH ranging from 10% to 20% of rearranged cells and were centre dependent. IHC remains a reliable pre-screening method for ALK rearrangement detection.
- Published
- 2015
48. Immunohistochemistry as a potential tool for routine detection of the NRAS Q61R mutation in patients with metastatic melanoma
- Author
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Marius Ilie, Elodie Long-Mira, Elisa Funck-Brentano, Sandra Lassalle, Catherine Butori, Virginie Lespinet-Fabre, Olivier Bordone, Alexandre Gay, Katia Zahaf, Gilles Poissonnet, Jean-Philippe Lacour, Philippe Bahadoran, Robert Ballotti, Audrey Gros, Caroline Dutriaux, Philippe Saiag, Jean-Philippe Merlio, Béatrice Vergier, Jean François Emile, Véronique Hofman, and Paul Hofman
- Subjects
Neuroblastoma RAS viral oncogene homolog ,Oncology ,Adult ,Male ,medicine.medical_specialty ,Pathology ,Skin Neoplasms ,medicine.drug_class ,Clone (cell biology) ,Dermatology ,Monoclonal antibody ,GTP Phosphohydrolases ,Cohort Studies ,Internal medicine ,medicine ,Humans ,Neoplasm Metastasis ,Melanoma ,Aged ,Retrospective Studies ,Aged, 80 and over ,biology ,business.industry ,Antibodies, Monoclonal ,Membrane Proteins ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Mutation (genetic algorithm) ,Mutation ,biology.protein ,Female ,Antibody ,business - Abstract
Background It can be useful to assess the NRAS mutation status in patients with metastatic melanoma because NRAS -activating mutations confer resistance to RAF inhibitors, and NRAS- mutated patients appear to be sensitive to mitogen-activated protein kinase (MEK) inhibitors. Objective We aimed to assess the diagnostic accuracy of an immunohistochemistry (IHC) approach using a novel anti-NRAS (Q61R) monoclonal antibody on formalin-fixed paraffin-embedded tissue samples from patients with metastatic melanoma. Methods We conducted a retrospective multicenter cohort study on 170 patients with metastatic melanoma. The automated IHC assay was performed using the SP174 clone, and compared with results of the molecular testing. Results Evaluation of a test cohort with knowledge of the mutation status established a specific IHC pattern for the mutation. In the independent blinded analysis of the remaining cases, the anti-NRAS (Q61R) antibody accurately identified all NRAS Q61R-mutated tumors, and demonstrated 100% sensitivity and specificity. Limitations Limitations include retrospective design and lack of multicenter interobserver reproducibility. Conclusion The NRAS (Q61R) IHC assay is reliable and specific for the evaluation of the Q61R mutation status in metastatic melanoma and may be an alternative to molecular biology in evaluation of metastatic melanoma in routine practice.
- Published
- 2014
49. Validation multicentrique des outils diagnostiques des réarrangements du gène ALK dans 547 adénocarcinomes pulmonaires
- Author
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Nathalie Monhoven, Françoise Galateau-Sallé, Marius Ilie, M. Shisheboran-Devouassoux, Hélène Blons, N. Le Stang, Isabelle Rouquette, Françoise Thivolet, Audrey Gros, Hugues Begueret, V. Grégoire, Anne McLeer-Florin, Frédérique Penault-Llorca, Sylvie Lantuejoul, J.-M. Vignaud, Audrey Mansuet-Lupo, Martine Antoine, Paul Hofman, and Stéphane Garcia
- Subjects
hemic and lymphatic diseases ,Anatomy - Abstract
Contexte Les rearrangements du gene ALK dans les adenocarcinomes pulmonaires (ADK) induisent une activation constitutive de la kinase ALK, ciblable par le crizotinib [1] , [2] . Bien que la FISH (hybridation in situ fluorescente) soit la technique de reference pour le diagnostic de ces rearrangements, l’immunohistochimie (IHC) pourrait etre utile en tant qu’outil de pre-screening. But de l’etude Comparer les techniques d’IHC, FISH et RT-qPCR ALK realisees par 14 plateformes de genetique moleculaire des cancers (PGMC). Materiel et methodes Pour cette etude methodologique, 547 ADK, enrichis en prelevements chirurgicaux et en cas positifs, ont ete analyses, en utilisant les anticorps 5A4 et D5F3 (IHC), 2 sondes break-apart (FISH), et des kits TaqMan (RT-qPCR), et les donnees clinicopathologiques des patients renseignees. Resultats Au total, 140 tumeurs presentaient un rearrangement du gene ALK par FISH (≥ 15 % de cellules rearrangees) et 400 etaient negatives ( 20 %. Aucun variant de transcription n’a ete detecte dans 36 % des cas ALK-positifs. Conclusion L’analyse des resultats a mis en evidence que les discordances IHC/FISH sont plus frequentes pour les cas « borderline » (FISH entre 10 et 20 %), et qu’elles sont PGMC-dependantes. L’IHC est donc un outil de prescreening fiable pour la detection des rearrangements du gene ALK.
- Published
- 2015
50. High-resolution array-CGH in patients with oculocutaneous albinism identifies new deletions of the TYR, OCA2, and SLC45A2 genes and a complex rearrangement of the OCA2 gene
- Author
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Audrey Gros, Eulalie Lasseaux, Benoit Arveiler, Caroline Rooryck, Brigitte Gilbert-Dussardier, Fanny Morice-Picard, Didier Lacombe, Josseline Kaplan, Delphine Simon, Stéphane François, Dorothée Cailley, Claudio Plaisant, and Jérôme Toutain
- Subjects
OCA2 ,Genetics ,SLC45A2 ,Comparative Genomic Hybridization ,Base Sequence ,Monophenol Monooxygenase ,Point mutation ,Intron ,Membrane Transport Proteins ,Dermatology ,Biology ,medicine.disease ,Oculocutaneous albinism ,General Biochemistry, Genetics and Molecular Biology ,Exon ,Oncology ,Albinism, Oculocutaneous ,Antigens, Neoplasm ,biology.protein ,medicine ,TYRP1 ,Gene ,Genome-Wide Association Study ,Sequence Deletion - Abstract
Summary Oculocutaneous albinism (OCA) is caused by mutations in six different genes, and their molecular diagnosis encompasses the search for point mutations and intragenic rearrangements. Here, we used high-resolution array-comparative genome hybridization (CGH) to search for rearrangements across exons, introns and regulatory sequences of four OCA genes: TYR, OCA2, TYRP1, and SLC45A2. We identified a total of ten new deletions in TYR, OCA2, and SLC45A2. A complex rearrangement of OCA2 was found in two unrelated patients. Whole-genome sequencing showed deletion of a 184-kb fragment (identical to a deletion previously found in Polish patients), whereby a large portion of the deleted sequence was re-inserted after severe reshuffling into intron 1 of OCA2. The high-resolution array-CGH presented here is a powerful tool to detect gene rearrangements. Finally, we review all known deletions of the OCA1–4 genes reported so far in the literature and show that deletions or duplications account for 5.6% of all mutations identified in the OCA1–4 genes.
- Published
- 2013
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