19 results on '"Le Gall, Jessica"'
Search Results
2. Male breast cancer: No evidence for mosaic BRCA1 promoter methylation involvement
- Author
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Schwartz, Mathias, primary, Ibadioune, Sabrina, additional, Vacher, Sophie, additional, Villy, Marie-Charlotte, additional, Trabelsi-Grati, Olfa, additional, Le Gall, Jessica, additional, Caputo, Sandrine M., additional, Delhomelle, Hélène, additional, Warcoin, Mathilde, additional, Moncoutier, Virginie, additional, Bourneix, Christine, additional, Boutry-Kryza, Nadia, additional, De Pauw, Antoine, additional, Stern, Marc-Henri, additional, Buecher, Bruno, additional, Mouret-Fourme, Emmanuelle, additional, Colas, Chrystelle, additional, Stoppa-Lyonnet, Dominique, additional, Masliah-Planchon, Julien, additional, Golmard, Lisa, additional, and Bieche, Ivan, additional
- Published
- 2023
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- View/download PDF
3. The clinical value of optical genome mapping in the rapid characterization of RB1 duplication and 15q23q24.2 triplication, for more appropriate prenatal genetic counselling.
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Bouassida, Malek, Molina‐Gomes, Denise, Koraichi, Fairouz, Hervé, Bérénice, Lhuilier, Morgane, Duvillier, Clémence, Le Gall, Jessica, Gauthier‐Villars, Marion, Serazin, Valérie, Quibel, Thibaud, Dard, Rodolphe, and Vialard, François
- Subjects
GENE mapping ,GENETIC counseling ,CHROMOSOMAL rearrangement ,CHROMOSOME abnormalities ,PRENATAL diagnosis ,CYTOGENETICS ,NUCLEOTIDE sequencing - Abstract
Background: Despite recent advances in prenatal genetic diagnosis, medical geneticists still face considerable difficulty in interpreting the clinical outcome of copy‐number‐variant duplications and defining the mechanisms underlying the formation of certain chromosomal rearrangements. Optical genome mapping (OGM) is an emerging cytogenomic tool with proved ability to identify the full spectrum of cytogenetic aberrations. Methods: Here, we report on the use of OGM in a prenatal diagnosis setting. Detailed breakpoint mapping was used to determine the relative orientations of triplicated and duplicated segments in two unrelated foetuses harbouring chromosomal aberrations: a de novo 15q23q24.2 triplication and a paternally inherited 13q14.2 duplication that overlapped partially with the RB1 gene. Results: OGM enabled us to suggest a plausible mechanism for the triplication and confirmed that the RB1 duplication was direct oriented and in tandem. This enabled us to predict the pathogenic consequences, refine the prognosis and adapt the follow‐up and familial screening appropriately. Conclusion: Along with an increase in diagnostic rates, OGM can rapidly highlight genotype–phenotype correlations, improve genetic counselling and significantly influence prenatal management. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. GermlineHPF1retrogene insertion inRB1gene involved in cancer predisposition
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Le Gall, Jessica, primary, Dehainault, Catherine, additional, Boutte, Matteo, additional, Petitalot, Ambre, additional, Caputo, Sandrine M, additional, Courtois, Laura, additional, Vacher, Sophie, additional, Bieche, Ivan, additional, Radvanyi, François, additional, Pacquement, Hélène, additional, Doz, François, additional, Lumbroso-Le Rouic, Livia, additional, Gauthier Villars, Marion, additional, Stoppa-Lyonnet, Dominique, additional, Lallemand, François, additional, Houdayer, Claude, additional, and Golmard, Lisa, additional
- Published
- 2023
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- View/download PDF
5. Expanding the phenotype of the X-linked BCOR microphthalmia syndromes
- Author
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Ragge, Nicola, Isidor, Bertrand, Bitoun, Pierre, Odent, Sylvie, Giurgea, Irina, Cogné, Benjamin, Deb, Wallid, Vincent, Marie, Le Gall, Jessica, Morton, Jenny, Lim, Derek, DDD Study, Le Meur, Guylène, Zazo Seco, Celia, Zafeiropoulou, Dimitra, Bax, Dorine, Zwijnenburg, Petra, Arteche, Anara, Swafiri, Saoud Tahsin, Cleaver, Ruth, McEntagart, Meriel, Kini, Usha, Newman, William, Ayuso, Carmen, Corton, Marta, Herenger, Yvan, Jeanne, Médéric, Calvas, Patrick, and Chassaing, Nicolas
- Published
- 2019
- Full Text
- View/download PDF
6. Male breast cancer: No evidence for mosaic BRCA1 promoter methylation involvement
- Author
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Schwartz, Mathias, Ibadioune, Sabrina, Vacher, Sophie, Villy, Marie-Charlotte, Trabelsi-Grati, Olfa, Le Gall, Jessica, Caputo, Sandrine M., Delhomelle, Hélène, Warcoin, Mathilde, Moncoutier, Virginie, Bourneix, Christine, Boutry-Kryza, Nadia, De Pauw, Antoine, Stern, Marc-Henri, Buecher, Bruno, Mouret-Fourme, Emmanuelle, Colas, Chrystelle, Stoppa-Lyonnet, Dominique, Masliah-Planchon, Julien, Golmard, Lisa, and Bieche, Ivan
- Published
- 2024
- Full Text
- View/download PDF
7. Germline HPF1 retrogene insertion in RB1 gene involved in cancer predisposition.
- Author
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Le Gall, Jessica, Dehainault, Catherine, Boutte, Matteo, Petitalot, Ambre, Caputo, Sandrine M., Courtois, Laura, Vacher, Sophie, Bieche, Ivan, Radvanyi, François, Pacquement, Hélène, Doz, François, Rouic, Livia Lumbroso-Le, Villars, Marion Gauthier, Stoppa-Lyonnet, Dominique, Lallemand, François, Houdayer, Claude, and Golmard, Lisa
- Abstract
About half of the human genome is composed of repeated sequences derived from mobile elements, mainly retrotransposons, generally without pathogenic effect. Familial forms of retinoblastoma are caused by germline pathogenic variants in RB1 gene. Here, we describe a family with retinoblastoma affecting a father and his son. No pathogenic variant was identified after DNA analysis of RB1 gene coding sequence and exonintron junctions. However, RB1 mRNA analysis showed a chimeric transcript with insertion of 114 nucleotides from HPF1 gene inside RB1 gene. This chimeric transcript led to an insertion of 38 amino acids in functional domain of retinoblastoma protein. Subsequent DNA analysis in RB1 intron 17 revealed the presence of a full-length HPF1 retrogene insertion in opposite orientation. Functional assay shows that this insertion has a deleterious impact on retinoblastoma protein function. This is the first report of a full-length retrogene insertion involved in human Mendelian disease leading to a chimeric transcript and a non-functional chimeric protein. Some retrogene insertions may be missed by standard diagnostic genetic testing, so contribution of retrogene insertions to human disease may be underestimated. The increasing use of whole genome sequencing in diagnostic settings will help to get a more comprehensive view of retrogenes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
8. Germline HPF1retrogene insertion in RB1gene involved in cancer predisposition
- Author
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Le Gall, Jessica, Dehainault, Catherine, Boutte, Matteo, Petitalot, Ambre, Caputo, Sandrine M, Courtois, Laura, Vacher, Sophie, Bieche, Ivan, Radvanyi, Francois, Pacquement, Hélène, Doz, Francois, Lumbroso-Le Rouic, Livia, Gauthier Villars, Marion, Stoppa-Lyonnet, Dominique, Lallemand, Francois, Houdayer, Claude, and Golmard, Lisa
- Abstract
About half of the human genome is composed of repeated sequences derived from mobile elements, mainly retrotransposons, generally without pathogenic effect. Familial forms of retinoblastoma are caused by germline pathogenic variants in RB1gene. Here, we describe a family with retinoblastoma affecting a father and his son. No pathogenic variant was identified after DNA analysis of RB1gene coding sequence and exon-intron junctions. However, RB1mRNA analysis showed a chimeric transcript with insertion of 114 nucleotides from HPF1gene inside RB1gene. This chimeric transcript led to an insertion of 38 amino acids in functional domain of retinoblastoma protein. Subsequent DNA analysis in RB1intron 17 revealed the presence of a full-length HPF1retrogene insertion in opposite orientation. Functional assay shows that this insertion has a deleterious impact on retinoblastoma protein function. This is the first report of a full-length retrogene insertion involved in human Mendelian disease leading to a chimeric transcript and a non-functional chimeric protein. Some retrogene insertions may be missed by standard diagnostic genetic testing, so contribution of retrogene insertions to human disease may be underestimated. The increasing use of whole genome sequencing in diagnostic settings will help to get a more comprehensive view of retrogenes.
- Published
- 2024
- Full Text
- View/download PDF
9. Diffuse Infiltrating Retinoblastoma with Anterior Chamber Involvement: Conservative Management and Identification of RB1 Alterations in Aqueous Humor.
- Author
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Cassoux, Nathalie, Malaise, Denis, Lumbroso-Le Rouic, Livia, Le Gall, Jessica, Golmard, Lisa, Cardoen, Liesbeth, Fréneaux, Paul, Bouchoucha, Yassine, Aerts, Isabelle, Doz, François, and Matet, Alexandre
- Published
- 2023
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- View/download PDF
10. APCgermline pathogenic variants and epithelial ovarian cancer: causal or coincidental findings?
- Author
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Vibert, Roseline, primary, Le Gall, Jessica, additional, Buecher, Bruno, additional, Mouret-Fourme, Emmanuelle, additional, Bataillon, Guillaume, additional, Becette, Véronique, additional, Trabelsi-Grati, Olfa, additional, Moncoutier, Virginie, additional, Dehainault, Catherine, additional, Carriere, Jennifer, additional, Schwartz, Mathias, additional, Suybeng, Voreak, additional, Bieche, Ivan, additional, Colas, Chrystelle, additional, Vincent-Salomon, Anne, additional, Stoppa-Lyonnet, Dominique, additional, and Golmard, Lisa, additional
- Published
- 2022
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11. Hereditary cancer predispositions: Comparison of multigene panel sequencing on fresh‐frozen breast/ovarian tumor versus blood.
- Author
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Schwartz, Mathias, Moncoutier, Virginie, Peytral, Adrien, Le Gall, Jessica, Suybeng, Voreak, Pagès, Mélanie, Masliah‐Planchon, Julien, Trabelsi‐Grati, Olfa, Melaabi, Samia, Callens, Céline, Bièche, Ivan, Delhomelle, Hélène, De Pauw, Antoine, Saule, Claire, Mouret‐Fourme, Emmanuelle, Gauthier‐Villars, Marion, Buecher, Bruno, Colas, Chrystelle, Stoppa‐Lyonnet, Dominique, and Golmard, Lisa
- Subjects
BREAST ,OVARIAN tumors ,DNA copy number variations ,GENE frequency ,OVARIAN cancer ,GERM cells - Abstract
In breast or ovarian cancer (BC/OC) patients with evocative personal and/or family history, multigene panel sequencing is performed on blood to diagnose hereditary predispositions. Additionally, BRCA1/BRCA2 testing can be performed on tumor sample for therapeutic purpose. The accuracy of multigene panel tumor analysis on BC/OC to detect predisposing germline pathogenic variants (gPV) has not been precisely assessed. By comparing sequencing data from blood and fresh‐frozen tumor we show that tumor genomic instability causes pitfalls to consider when performing tumor testing to detect gPV. Even if loss of heterozygosity increases germline signal in most cases, somatic copy number variants (CNV) can mask germline CNV and collapse point gPV variant allele frequency (VAF). Moreover, VAF does not allow an accurate distinction between germline and somatic pathogenic variants. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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- View/download PDF
12. APC germline pathogenic variants and epithelial ovarian cancer: causal or coincidental findings?
- Author
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Vibert, Roseline, Le Gall, Jessica, Buecher, Bruno, Mouret-Fourme, Emmanuelle, Bataillon, Guillaume, Becette, Véronique, Trabelsi-Grati, Olfa, Moncoutier, Virginie, Dehainault, Catherine, Carriere, Jennifer, Schwartz, Mathias, Suybeng, Voreak, Bieche, Ivan, Colas, Chrystelle, Vincent-Salomon, Anne, Stoppa-Lyonnet, Dominique, and Golmard, Lisa
- Abstract
APC germline pathogenic variants result in predisposition to familial adenomatous polyposis and extraintestinal tumours such as desmoid fibromatosis, medulloblastomas and thyroid cancers. They have also been recently involved in ovarian microcystic stromal tumours. APC inactivation has been described at the tumour level in epithelial ovarian cancers (EOCs). Here, we report the identification of APC germline pathogenic variants in two patients diagnosed with premenopausal EOC in early 30s, with no other pathogenic variant detected in the known ovarian cancer predisposing genes. Subsequent tumour analysis showed neither a second hit of APC inactivation nor β-catenin activation. Both tumours did not have a homologous recombination (HR) deficiency, pointing towards the implication of other genes than those involved in HR. APC may contribute to the carcinogenesis of EOC in a multifactorial context. Further studies are required to clarify the role of APC in predisposition to EOC. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
13. Diffuse Infiltrating Retinoblastoma with Anterior Chamber Involvement: Conservative Management and Identification of RB1Alterations in Aqueous Humor
- Author
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Cassoux, Nathalie, Malaise, Denis, Lumbroso-Le Rouic, Livia, Le Gall, Jessica, Golmard, Lisa, Cardoen, Liesbeth, Fréneaux, Paul, Bouchoucha, Yassine, Aerts, Isabelle, Doz, François, and Matet, Alexandre
- Abstract
Introduction:The aim of the study was to describe the successful conservative management of diffuse infiltrating retinoblastoma (DIR). Identification of RB1pathogenic variant was done after cell-free DNA (cfDNA) analysis in aqueous humor. Case presentation:Herein, we report 2 patients with unilateral, non-familial DIR with anterior and posterior involvement. Both patients underwent liquid biopsy for tumor cfDNA analysis in aqueous humor. Treatment consisted of a combination of systemic and intra-arterial chemotherapy, with consecutive intracameral and intravitreal injections of melphalan. One patient also required iodine-125 brachytherapy. In both cases, tumor cfDNA analysis revealed biallelic somatic alterations of the RB1gene. These alterations were not found in germline DNA. Both patients retained their eyes and had a useful vision after a follow-up of 2 years. Conclusion:In selected cases, conservative management of DIR is safe and effective. Tumor cfDNA analysis in aqueous humor is an effective technique to disclose RB1somatic alterations that guide the germline molecular explorations and improve genetic counseling after conservative treatment.
- Published
- 2023
- Full Text
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14. Highly Sensitive Detection Method of Retinoblastoma Genetic Predisposition and Biomarkers
- Author
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Le Gall, Jessica, primary, Dehainault, Catherine, additional, Benoist, Camille, additional, Matet, Alexandre, additional, Lumbroso-Le Rouic, Livia, additional, Aerts, Isabelle, additional, Jiménez, Irene, additional, Schleiermacher, Gudrun, additional, Houdayer, Claude, additional, Radvanyi, François, additional, Frouin, Eleonore, additional, Renault, Victor, additional, Doz, François, additional, Stoppa-Lyonnet, Dominique, additional, Gauthier-Villars, Marion, additional, Cassoux, Nathalie, additional, and Golmard, Lisa, additional
- Published
- 2021
- Full Text
- View/download PDF
15. APCgermline pathogenic variants and epithelial ovarian cancer: causal or coincidental findings?
- Author
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Vibert, Roseline, Le Gall, Jessica, Buecher, Bruno, Mouret-Fourme, Emmanuelle, Bataillon, Guillaume, Becette, Véronique, Trabelsi-Grati, Olfa, Moncoutier, Virginie, Dehainault, Catherine, Carriere, Jennifer, Schwartz, Mathias, Suybeng, Voreak, Bieche, Ivan, Colas, Chrystelle, Vincent-Salomon, Anne, Stoppa-Lyonnet, Dominique, and Golmard, Lisa
- Abstract
APCgermline pathogenic variants result in predisposition to familial adenomatous polyposis and extraintestinal tumours such as desmoid fibromatosis, medulloblastomas and thyroid cancers. They have also been recently involved in ovarian microcystic stromal tumours. APCinactivation has been described at the tumour level in epithelial ovarian cancers (EOCs). Here, we report the identification of APCgermline pathogenic variants in two patients diagnosed with premenopausal EOC in early 30s, with no other pathogenic variant detected in the known ovarian cancer predisposing genes. Subsequent tumour analysis showed neither a second hit of APCinactivation nor β-catenin activation. Both tumours did not have a homologous recombination (HR) deficiency, pointing towards the implication of other genes than those involved in HR. APCmay contribute to the carcinogenesis of EOC in a multifactorial context. Further studies are required to clarify the role of APCin predisposition to EOC.
- Published
- 2023
- Full Text
- View/download PDF
16. Expanding the phenotype of the X-linked BCOR microphthalmia syndromes
- Author
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Ragge, Nicola, Isidor, Bertrand, Bitoun, Pierre, OdentIrina Giurgea, Sylvie, Cogné, Benjamin, Deb, Wallid, Marie, Vincent, Le Gall, Jessica, Morton, Jenny, Lim, Derek, Le Meur, Guylène, Zazo Seco, Celia, Zafeiropoulou, Dimitra, Bax, Dorine, Zwijnenburg, Petra, Arteche, Anara, Tahsin Swafiri , Saoud, Cleaver, Ruth, McEntagart, Meriel, Kini, Usha, Newman, William, Ayuso, Carmen, Corton, Marta, Herenger, Yvan, Jeanne, Médéric, Calvas, Patrick, Chassaing, Nicolas, Ragge, Nicola, Isidor, Bertrand, Bitoun, Pierre, OdentIrina Giurgea, Sylvie, Cogné, Benjamin, Deb, Wallid, Marie, Vincent, Le Gall, Jessica, Morton, Jenny, Lim, Derek, Le Meur, Guylène, Zazo Seco, Celia, Zafeiropoulou, Dimitra, Bax, Dorine, Zwijnenburg, Petra, Arteche, Anara, Tahsin Swafiri , Saoud, Cleaver, Ruth, McEntagart, Meriel, Kini, Usha, Newman, William, Ayuso, Carmen, Corton, Marta, Herenger, Yvan, Jeanne, Médéric, Calvas, Patrick, and Chassaing, Nicolas
- Abstract
Two distinct syndromes arise from pathogenic variants in the X-linked gene BCOR (BCL-6 corepressor): oculofaciocardiodental (OFCD) syndrome, which affects females, and a severe microphthalmia (‘Lenz’-type) syndrome affecting males. OFCD is an X-linked dominant syndrome caused by a variety of BCOR null mutations. As it manifests only in females, it is presumed to be lethal in males. The severe male X-linked recessive microphthalmia syndrome (‘Lenz’) usually includes developmental delay in addition to the eye findings and is caused by hypomorphic BCOR variants, mainly by a specific missense variant c.254C > T, p.(Pro85Leu). Here, we detail 16 new cases (11 females with 4 additional, genetically confirmed, affected female relatives; 5 male cases each with unaffected carrier mothers). We describe new variants and broaden the phenotypic description for OFCD to include neuropathy, muscle hypotonia, pituitary underdevelopment, brain atrophy, lipoma and the first description of childhood lymphoma in an OFCD case. Our male X-linked recessive cases show significant new phenotypes: developmental delay (without eye anomalies) in two affected half-brothers with a novel BCOR variant, and one male with high myopia, megalophthalmos, posterior embryotoxon, developmental delay, and heart and bony anomalies with a previously undescribed BCOR splice site variant. Our female OFCD cases and their affected female relatives showed variable features, but consistently had early onset cataracts. We show that a mosaic carrier mother manifested early cataract and dental anomalies. All female carriers of the male X-linked recessive cases for whom genetic confirmation was available showed skewed X-inactivation and were unaffected. In view of the extended phenotype, we suggest a new term of X-linked BCOR-related syndrome.
- Published
- 2018
17. Sex chromosome aneuploidies and copy-number variants: a further explanation for neurodevelopmental prognosis variability?
- Author
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Le Gall, Jessica, primary, Nizon, Mathilde, additional, Pichon, Olivier, additional, Andrieux, Joris, additional, Audebert-Bellanger, Séverine, additional, Baron, Sabine, additional, Beneteau, Claire, additional, Bilan, Frédéric, additional, Boute, Odile, additional, Busa, Tiffany, additional, Cormier-Daire, Valérie, additional, Ferec, Claude, additional, Fradin, Mélanie, additional, Gilbert-Dussardier, Brigitte, additional, Jaillard, Sylvie, additional, Jønch, Aia, additional, Martin-Coignard, Dominique, additional, Mercier, Sandra, additional, Moutton, Sébastien, additional, Rooryck, Caroline, additional, Schaefer, Elise, additional, Vincent, Marie, additional, Sanlaville, Damien, additional, Le Caignec, Cédric, additional, Jacquemont, Sébastien, additional, David, Albert, additional, and Isidor, Bertrand, additional
- Published
- 2017
- Full Text
- View/download PDF
18. Germline HPF1 retrogene insertion in RB1 gene involved in cancer predisposition.
- Author
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Le Gall J, Dehainault C, Boutte M, Petitalot A, Caputo SM, Courtois L, Vacher S, Bieche I, Radvanyi F, Pacquement H, Doz F, Lumbroso-Le Rouic L, Gauthier Villars M, Stoppa-Lyonnet D, Lallemand F, Houdayer C, and Golmard L
- Subjects
- Humans, Retinoblastoma Protein genetics, Genes, Retinoblastoma, Disease Susceptibility, DNA, DNA Mutational Analysis, Ubiquitin-Protein Ligases genetics, Retinoblastoma Binding Proteins genetics, Carrier Proteins genetics, Nuclear Proteins genetics, Retinoblastoma genetics, Retinoblastoma diagnosis, Retinoblastoma pathology, Retinal Neoplasms diagnosis, Retinal Neoplasms genetics, Retinal Neoplasms pathology
- Abstract
About half of the human genome is composed of repeated sequences derived from mobile elements, mainly retrotransposons, generally without pathogenic effect. Familial forms of retinoblastoma are caused by germline pathogenic variants in RB1 gene. Here, we describe a family with retinoblastoma affecting a father and his son. No pathogenic variant was identified after DNA analysis of RB1 gene coding sequence and exon-intron junctions. However, RB1 mRNA analysis showed a chimeric transcript with insertion of 114 nucleotides from HPF1 gene inside RB1 gene. This chimeric transcript led to an insertion of 38 amino acids in functional domain of retinoblastoma protein. Subsequent DNA analysis in RB1 intron 17 revealed the presence of a full-length HPF1 retrogene insertion in opposite orientation. Functional assay shows that this insertion has a deleterious impact on retinoblastoma protein function. This is the first report of a full-length retrogene insertion involved in human Mendelian disease leading to a chimeric transcript and a non-functional chimeric protein. Some retrogene insertions may be missed by standard diagnostic genetic testing, so contribution of retrogene insertions to human disease may be underestimated. The increasing use of whole genome sequencing in diagnostic settings will help to get a more comprehensive view of retrogenes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
- Full Text
- View/download PDF
19. Classification of 101 BRCA1 and BRCA2 variants of uncertain significance by cosegregation study: A powerful approach.
- Author
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Caputo SM, Golmard L, Léone M, Damiola F, Guillaud-Bataille M, Revillion F, Rouleau E, Derive N, Buisson A, Basset N, Schwartz M, Vilquin P, Garrec C, Privat M, Gay-Bellile M, Abadie C, Abidallah K, Airaud F, Allary AS, Barouk-Simonet E, Belotti M, Benigni C, Benusiglio PR, Berthemin C, Berthet P, Bertrand O, Bézieau S, Bidart M, Bignon YJ, Birot AM, Blanluet M, Bloucard A, Bombled J, Bonadona V, Bonnet F, Bonnet-Dupeyron MN, Boulaire M, Boulouard F, Bouras A, Bourdon V, Brahimi A, Brayotel F, Bressac de Paillerets B, Bronnec N, Bubien V, Buecher B, Cabaret O, Carriere J, Chiesa J, Chieze-Valéro S, Cohen C, Cohen-Haguenauer O, Colas C, Collonge-Rame MA, Conoy AL, Coulet F, Coupier I, Crivelli L, Cusin V, De Pauw A, Dehainault C, Delhomelle H, Delnatte C, Demontety S, Denizeau P, Devulder P, Dreyfus H, d'Enghein CD, Dupré A, Durlach A, Dussart S, Fajac A, Fekairi S, Fert-Ferrer S, Fiévet A, Fouillet R, Mouret-Fourme E, Gauthier-Villars M, Gesta P, Giraud S, Gladieff L, Goldbarg V, Goussot V, Guibert V, Guillerm E, Guy C, Hardouin A, Heude C, Houdayer C, Ingster O, Jacquot-Sawka C, Jones N, Krieger S, Lacoste S, Lallaoui H, Larbre H, Laugé A, Le Guyadec G, Le Mentec M, Lecerf C, Le Gall J, Legendre B, Legrand C, Legros A, Lejeune S, Lidereau R, Lignon N, Limacher JM, Doriane Livon, Lizard S, Longy M, Lortholary A, Macquere P, Mailliez A, Malsa S, Margot H, Mari V, Maugard C, Meira C, Menjard J, Molière D, Moncoutier V, Moretta-Serra J, Muller E, Nevière Z, Nguyen Minh Tuan TV, Noguchi T, Noguès C, Oca F, Popovici C, Prieur F, Raad S, Rey JM, Ricou A, Salle L, Saule C, Sevenet N, Simaga F, Sobol H, Suybeng V, Tennevet I, Tenreiro H, Tinat J, Toulas C, Turbiez I, Uhrhammer N, Vande Perre P, Vaur D, Venat L, Viellard N, Villy MC, Warcoin M, Yvard A, Zattara H, Caron O, Lasset C, Remenieras A, Boutry-Kryza N, Castéra L, and Stoppa-Lyonnet D
- Subjects
- Breast Neoplasms classification, Breast Neoplasms genetics, Female, Genetic Testing, Genotype, Humans, Ovarian Neoplasms classification, Ovarian Neoplasms genetics, BRCA1 Protein genetics, BRCA2 Protein genetics, Breast Neoplasms pathology, Genetic Predisposition to Disease, Genetic Variation, Ovarian Neoplasms pathology
- Abstract
Up to 80% of BRCA1 and BRCA2 genetic variants remain of uncertain clinical significance (VUSs). Only variants classified as pathogenic or likely pathogenic can guide breast and ovarian cancer prevention measures and treatment by PARP inhibitors. We report the first results of the ongoing French national COVAR (cosegregation variant) study, the aim of which is to classify BRCA1/2 VUSs. The classification method was a multifactorial model combining different associations between VUSs and cancer, including cosegregation data. At this time, among the 653 variants selected, 101 (15%) distinct variants shared by 1,624 families were classified as pathogenic/likely pathogenic or benign/likely benign by the COVAR study. Sixty-six of the 101 (65%) variants classified by COVAR would have remained VUSs without cosegregation data. Of note, among the 34 variants classified as pathogenic by COVAR, 16 remained VUSs or likely pathogenic when following the ACMG/AMP variant classification guidelines. Although the initiation and organization of cosegregation analyses require a considerable effort, the growing number of available genetic tests results in an increasing number of families sharing a particular variant, and thereby increases the power of such analyses. Here we demonstrate that variant cosegregation analyses are a powerful tool for the classification of variants in the BRCA1/2 breast-ovarian cancer predisposition genes., Competing Interests: Declaration of interests D.S.-L. and the Institut Curie have received honoraria for her participation in education meetings organized by AstraZeneca or Tesaro. The remaining authors declare no conflict of interest., (Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
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