Almost 2% of Spanish breast cancer families are associated to germline pathogenic mutations in the ATM gene.

Autor: Tavera-Tapia A; Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Melchor Fernández Almagro 3, 28029, Madrid, Spain., Pérez-Cabornero L; Medical Genetics Unit, Sistemas Genómicos, Parque Tecnológico de Valencia, Ronda G. Marconi 6, 46980, Paterna, Spain., Macías JA; Hereditary Cancer Unit, Medical Oncology Service, Hospital Morales Meseguer, Av Marqués de los Vélez, s/n, 30008, Murcia, Spain., Ceballos MI; Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Melchor Fernández Almagro 3, 28029, Madrid, Spain., Roncador G; Monoclonal Antibody Unit, Spanish National Cancer Research Centre, Melchor Fernández Almagro 3, 28029, Madrid, Spain., de la Hoya M; Molecular Oncology Laboratory, Hospital Clínico San Carlos, IdISSC, Calle del Prof Martín Lagos, s/n, 28040, Madrid, Spain., Barroso A; Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Melchor Fernández Almagro 3, 28029, Madrid, Spain., Felipe-Ponce V; Medical Genetics Unit, Sistemas Genómicos, Parque Tecnológico de Valencia, Ronda G. Marconi 6, 46980, Paterna, Spain., Serrano-Blanch R; Medical Oncology Department, Hospital Reina Sofía, Av. Menéndez Pidal s/n, 14004, Córdoba, Spain., Hinojo C; Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Av. de Valdecilla, s/n, 39008, Santander, Spain., Miramar-Gallart MD; Medical Genetics Unit, Biochemistry Service, Miguel Servet Hospital, Paseo Isabel la Católica, 1-3, 50009, Saragossa, Spain., Urioste M; Familial Cancer Clinical Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Melchor Fernández Almagro 3, 28029, Madrid, Spain., Caldés T; Molecular Oncology Laboratory, Hospital Clínico San Carlos, IdISSC, Calle del Prof Martín Lagos, s/n, 28040, Madrid, Spain., Santillan-Garzón S; Medical Genetics Unit, Sistemas Genómicos, Parque Tecnológico de Valencia, Ronda G. Marconi 6, 46980, Paterna, Spain., Benitez J; Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Melchor Fernández Almagro 3, 28029, Madrid, Spain.; Spanish Network on Rare Diseases (CIBERER), Monforte de Lemos 3-5. Pabellón 11. Planta 0, 28029, Madrid, Spain.; Genotyping Unit, CEGEN, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Melchor Fernández Almagro 3, 28029, Madrid, Spain., Osorio A; Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Melchor Fernández Almagro 3, 28029, Madrid, Spain. aosorio@cnio.es.; Spanish Network on Rare Diseases (CIBERER), Monforte de Lemos 3-5. Pabellón 11. Planta 0, 28029, Madrid, Spain. aosorio@cnio.es.
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2017 Feb; Vol. 161 (3), pp. 597-604. Date of Electronic Publication: 2016 Dec 02.
DOI: 10.1007/s10549-016-4058-7
Abstrakt: 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.
Databáze: MEDLINE
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