A Tavera-Tapia1, L Pérez-Cabornero2, J A Macías3, M I Ceballos1, G Roncador4, M de la Hoya5, A Barroso1, V Felipe-Ponce2, R Serrano-Blanch6, C Hinojo7, M D Miramar-Gallart8, M Urioste9, T Caldés5, S Santillan-Garzón2, J Benitez1,10,11, A Osorio12,13. 1. Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Melchor Fernández Almagro 3, 28029, Madrid, Spain. 2. Medical Genetics Unit, Sistemas Genómicos, Parque Tecnológico de Valencia, Ronda G. Marconi 6, 46980, Paterna, Spain. 3. Hereditary Cancer Unit, Medical Oncology Service, Hospital Morales Meseguer, Av Marqués de los Vélez, s/n, 30008, Murcia, Spain. 4. Monoclonal Antibody Unit, Spanish National Cancer Research Centre, Melchor Fernández Almagro 3, 28029, Madrid, Spain. 5. Molecular Oncology Laboratory, Hospital Clínico San Carlos, IdISSC, Calle del Prof Martín Lagos, s/n, 28040, Madrid, Spain. 6. Medical Oncology Department, Hospital Reina Sofía, Av. Menéndez Pidal s/n, 14004, Córdoba, Spain. 7. Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Av. de Valdecilla, s/n, 39008, Santander, Spain. 8. Medical Genetics Unit, Biochemistry Service, Miguel Servet Hospital, Paseo Isabel la Católica, 1-3, 50009, Saragossa, Spain. 9. Familial Cancer Clinical Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Melchor Fernández Almagro 3, 28029, Madrid, Spain. 10. Spanish Network on Rare Diseases (CIBERER), Monforte de Lemos 3-5. Pabellón 11. Planta 0, 28029, Madrid, Spain. 11. Genotyping Unit, CEGEN, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Melchor Fernández Almagro 3, 28029, Madrid, Spain. 12. Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Melchor Fernández Almagro 3, 28029, Madrid, Spain. aosorio@cnio.es. 13. Spanish Network on Rare Diseases (CIBERER), Monforte de Lemos 3-5. Pabellón 11. Planta 0, 28029, Madrid, Spain. aosorio@cnio.es.
Abstract
PURPOSE: There is still a considerable percentage of hereditary breast and ovarian cancer (HBOC) cases not explained by BRCA1 and BRCA2 genes. In this report, next-generation sequencing (NGS) techniques were applied to identify novel variants and/or genes involved in HBOC susceptibility. METHODS: Using whole exome sequencing, we identified a novel germline mutation in the moderate-risk gene ATM (c.5441delT; p.Leu1814Trpfs*14) in a family negative for mutations in BRCA1/2 (BRCAX). A case-control association study was performed to establish its prevalence in Spanish population, in a series of 1477 BRCAX families and 589 controls further screened, and NGS panels were used for ATM mutational screening in a cohort of 392 HBOC Spanish BRCAX families and 350 patients affected with diseases not related to breast cancer. RESULTS: Although the interrogated mutation was not prevalent in case-control association study, a comprehensive mutational analysis of the ATM gene revealed 1.78% prevalence of mutations in the ATM gene in HBOC and 1.94% in breast cancer-only BRCAX families in Spanish population, where data about ATM mutations were very limited. CONCLUSION: ATM mutation prevalence in Spanish population highlights the importance of considering ATM pathogenic variants linked to breast cancer susceptibility.
PURPOSE: There is still a considerable percentage of hereditary breast and ovarian cancer (HBOC) cases not explained by BRCA1 and BRCA2 genes. In this report, next-generation sequencing (NGS) techniques were applied to identify novel variants and/or genes involved in HBOC susceptibility. METHODS: Using whole exome sequencing, we identified a novel germline mutation in the moderate-risk gene ATM (c.5441delT; p.Leu1814Trpfs*14) in a family negative for mutations in BRCA1/2 (BRCAX). A case-control association study was performed to establish its prevalence in Spanish population, in a series of 1477 BRCAX families and 589 controls further screened, and NGS panels were used for ATM mutational screening in a cohort of 392 HBOC Spanish BRCAX families and 350 patients affected with diseases not related to breast cancer. RESULTS: Although the interrogated mutation was not prevalent in case-control association study, a comprehensive mutational analysis of the ATM gene revealed 1.78% prevalence of mutations in the ATM gene in HBOC and 1.94% in breast cancer-only BRCAX families in Spanish population, where data about ATM mutations were very limited. CONCLUSION:ATM mutation prevalence in Spanish population highlights the importance of considering ATM pathogenic variants linked to breast cancer susceptibility.
Entities:
Keywords:
ATM; Germline pathogenic variant; Hereditary breast and ovarian cancer; Whole exome sequencing
Authors: Alisa M Goldstein; Elizabeth M Gillanders; Melissa Rotunno; Rolando Barajas; Mindy Clyne; Elise Hoover; Naoko I Simonds; Tram Kim Lam; Leah E Mechanic Journal: Cancer Epidemiol Biomarkers Prev Date: 2020-05-28 Impact factor: 4.254
Authors: Fabienne Lesueur; Douglas F Easton; Anne-Laure Renault; Sean V Tavtigian; Jonine L Bernstein; Zsofia Kote-Jarai; Rosalind A Eeles; Dijana Plaseska-Karanfia; Lidia Feliubadaló; Banu Arun; Natalie Herold; Beatrix Versmold; Rita Katharina Schmutzler; Tú Nguyen-Dumont; Melissa C Southey; Leila Dorling; Alison M Dunning; Paola Ghiorzo; Bruna Samia Dalmasso; Eve Cavaciuti; Dorothée Le Gal; Nicholas J Roberts; Mev Dominguez-Valentin; Matti Rookus; Alexander M R Taylor; Alisa M Goldstein; David E Goldgar; Dominique Stoppa-Lyonnet; Nadine Andrieu Journal: Fam Cancer Date: 2021-06-14 Impact factor: 2.375