6 results on '"Collura, Ada"'
Search Results
2. Extensive characterization of sphere models established from colorectal cancer cell lines
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Collura, Ada, Marisa, Laetitia, Trojan, Diletta, Buhard, Olivier, Lagrange, Anaïs, Saget, Arnaud, Bombled, Marianne, Méchighel, Patricia, Ayadi, Mira, Muleris, Martine, de Reynies, Aurélien, Svrcek, Magali, Fléjou, Jean-François, Florent, Jean-Claude, Mahuteau-Betzer, Florence, Faussat, Anne-Marie, and Duval, Alex
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- 2013
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3. Identification of Positively and Negatively Selected Driver Gene Mutations Associated With Colorectal Cancer With Microsatellite Instability Positive Selection Pressure Mutational Background Negative Selection Pressure Mutational Frequency Microsatellite length (bp)
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Jonchère, Vincent, Marisa, Laetitia, Greene, Malorie, Virouleau, Alain, Buhard, Olivier, Bertrand, Romane, Svrcek, Magali, Cervera, Pascale, Goloudina, Anastasia, Guillerm, Erell, Coulet, Florence, Landman, Samuel, Ratovomanana, Toky, Job, Sylvie, Ayadi, Mira, Elarouci, Nabila, Armenoult, Lucile, Merabtene, Fatiha, Dumont, Sylvie, Parc, Yann, Lefèvre, Jérémie, André, Thierry, Fléjou, Jean-François, Guilloux, Agathe, Collura, Ada, De Reynies, Aurélien, Duval, Alex, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Ligue Nationale Contre le Cancer - Paris, Ligue Nationnale Contre le Cancer, Laboratoire de Mathématiques et Modélisation d'Evry (LaMME), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-ENSIIE-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Unité Mixte de Service d'Imagerie et de Cytométrie (UMS LUMIC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Oncologie Médicale [CHU Saint -Antoine], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Sorbonne Université (SU)-CHU Saint-Antoine [APHP], Service de génétique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Ligue Nationale Contre le Cancer (LNCC), and CHU Saint-Antoine [AP-HP]
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Colorectal Cancer ,Driver Gene Mutations ,Positive and Negative Selection ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Microsatellite Instability ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,neoplasms ,digestive system diseases ,Tumorigenic Process - Abstract
International audience; Background & Aims: Recent studies have shown that cancers arise as a result of the positive selection of driver somatic events in tumor DNA, with negative selection playing only a minor role, if any. However, these investigations were concerned with alterations at nonrepetitive sequences and did not take into account mutations in repetitive sequences that have very high pathophysiological relevance in the tumors showing microsatellite instability (MSI) resulting from mismatch repair deficiency investigated in the present study.Methods: We performed whole-exome sequencing of 47 MSI colorectal cancers (CRCs) and confirmed results in an independent cohort of 53 MSI CRCs. We used a probabilistic model of mutational events within microsatellites, while adapting pre-existing models to analyze nonrepetitive DNA sequences. Negatively selected coding alterations in MSI CRCs were investigated for their functional and clinical impact in CRC cell lines and in a third cohort of 164 MSI CRC patients.Results: Both positive and negative selection of somatic mutations in DNA repeats was observed, leading us to identify the expected true driver genes associated with the MSI-driven tumorigenic process. Several coding negatively selected MSI-related mutational events (n = 5) were shown to have deleterious effects on tumor cells. In the tumors in which deleterious MSI mutations were observed despite the negative selection, they were associated with worse survival in MSI CRC patients (hazard ratio, 3; 95% CI, 1.1-7.9; P = .03), suggesting their anticancer impact should be offset by other as yet unknown oncogenic processes that contribute to a poor prognosis.Conclusions: The present results identify the positive and negative driver somatic mutations acting in MSI-driven tumorigenesis, suggesting that genomic instability in MSI CRC plays a dual role in achieving tumor cell transformation. Exome sequencing data have been deposited in the European genome-phenome archive (accession: EGAS00001002477).
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- 2018
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4. Major improvement in the detection of microsatellite instability in colorectal cancer using HSP110 T17 E‐<italic>ice</italic>‐COLD‐PCR.
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How‐Kit, Alexandre, Daunay, Antoine, Buhard, Olivier, Meiller, Clément, Sahbatou, Mourad, Collura, Ada, Duval, Alex, and Deleuze, Jean‐François
- Abstract
Abstract: Every colorectal cancer (CRC) patient should be tested for microsatellite instability (MSI) to screen for Lynch syndrome. Evaluation of MSI status involves screening tumor DNA for the presence of somatic deletions in DNA repeats using PCR followed by fragment analysis. While this method may lack sensitivity due to the presence of a high level of germline DNA, which frequently contaminates the core of primary colon tumors, no other method developed to date is capable of modifying the standard PCR protocol to achieve improvement of MSI detection. Here, we describe a new approach developed for the ultra‐sensitive detection of MSI in CRC based on E‐
ice ‐COLD‐PCR, using HSP110 T17, a mononucleotide DNA repeat previously proposed as an optimal marker to detect MSI in tumor DNA, and an oligo(dT)16 LNA blocker probe complementary to wild‐type genotypes. The HT17 E‐ice ‐COLD‐PCR assay improved MSI detection by 20–200‐fold compared with standard PCR using HT17 alone. It presents an analytical sensitivity of 0.1%–0.05% of mutant alleles in wild‐type background, thus greatly improving MSI detection in CRC samples highly contaminated with normal DNA. HT17 E‐ice ‐COLD‐PCR is a rapid, cost‐effective, easy‐to‐implement, and highly sensitive method, which could significantly improve the detection of MSI in routine clinical testing. [ABSTRACT FROM AUTHOR]- Published
- 2018
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5. The Balance Between Cytotoxic T-cell Lymphocytes and Immune Checkpoint Expression in the Prognosis of Colon Tumors.
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Marisa, Laetitia, Svrcek, Magali, Collura, Ada, Becht, Etienne, Cervera, Pascale, Wanherdrick, Kristell, Buhard, Olivier, Goloudina, Anastasia, Jonchère, Vincent, Selves, Janick, Milano, Gerard, Guenot, Dominique, Cohen, Romain, Colas, Chrystelle, Laurent-Puig, Pierre, Olschwang, Sylviane, Lefévre, Jérémie H., Parc, Yann, Ghiringhelli, François, and de Reynies, Aurélien
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ANTIGEN analysis ,ANTIGENS ,COLON (Anatomy) ,COLON tumors ,COMPARATIVE studies ,DEGENERATION (Pathology) ,GENE expression ,LYMPHOCYTES ,RESEARCH methodology ,MEDICAL cooperation ,PROGNOSIS ,RECTUM tumors ,RESEARCH ,SURVIVAL ,T cells ,TUMOR classification ,EVALUATION research ,RETROSPECTIVE studies - Abstract
Background: Immune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore.Methods: The expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI). Their associations with patient survival were analyzed by Cox models, taking into account the microsatellite instability (MSI) status and affiliation with various Consensus Molecular Subgroups (CMS). PD-L1 and CD8 expression were examined on a subset of tumors with immunohistochemistry. All statistical tests were two-sided.Results: The expression of Immunoscore-like metagenes was statistically significantly associated with improved outcome in non-MSI tumors displaying low levels of both CTLs and immune checkpoints (ICKs; CMS2 and CMS3; hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.43 to 0.92, P = .02; and HR = 0.55, 95% CI = 0.34 to 0.90, P = .02, respectively), but clearly had no prognostic relevance in CRCs displaying higher levels of CTLs and ICKs (CMS1 and CMS4; HR = 0.46, 95% CI = 0.10 to 2.10, P = .32; and HR = 1.13, 95% CI = 0.79 to 1.63, P = .50, respectively), including MSI tumors. ICK metagene expression was statistically significantly associated with worse prognosis independent of tumor staging in MSI tumors (HR = 3.46, 95% CI = 1.41 to 8.49, P = .007). ICK expression had a negative impact on the proliferation of infiltrating CD8 T cells in MSI neoplasms (median = 0.56 in ICK low vs median = 0.34 in ICK high, P = .004).Conclusions: ICK expression cancels the prognostic relevance of CTLs in highly immunogenic colon tumors and predicts a poor outcome in MSI CRC patients. [ABSTRACT FROM AUTHOR]- Published
- 2018
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6. Primary Resistance to Immune Checkpoint Inhibitors in Metastatic Colorectal Cancer-Beyond the Misdiagnosis-In Reply
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Alex Duval, Magali Svrcek, Romain Cohen, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Site de recherche intégrée en cancérologie (SiRIC CURAMUS), Institut Universitaire de Cancérologie [Paris] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Collura, Ada
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Cancer Research ,Colorectal cancer ,business.industry ,Brain Neoplasms ,Immune checkpoint inhibitors ,[SDV]Life Sciences [q-bio] ,MEDLINE ,Microsatellite instability ,medicine.disease ,[SDV] Life Sciences [q-bio] ,Oncology ,Neoplastic Syndromes, Hereditary ,Cancer research ,medicine ,Humans ,Microsatellite Instability ,Diagnostic Errors ,business ,Colorectal Neoplasms - Abstract
International audience; No abstract available
- Published
- 2019
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