Comprehensive Analysis of Germline Variants in Mexican Patients with Hereditary Breast and Ovarian Cancer Susceptibility

• Type of Material: Article
• Authors: Rosalia Quezada Urban, Facultad de Estudios Superiores Iztacala; Clara Estela Diaz Velasquez, Facultad de Estudios Superiores Iztacala; Rina Gitler, Fundacion Alma; Maria Patricia Rojo Castillo, Fundacion Alma; Max Sirota Toporek, Fundacion Alma; Andrea Figueroa Morales, Fundacion Alma; Oscar Moreno Garcia, Fundacion Alma; Lizbeth Garcia Esquivel, Fundacion Alma; Gabriela Torres Mejia, Instituto Nacional de Salud Publica; Michael Dean, National Cancer Institute; Ivan Delgado Enciso, Instituto Estatal de Cancerologia de Colima; Hector Ochoa Diaz Lopez, El Colegio de la Frontera Sur; Fernando Rodriguez Leon, El Colegio de la Frontera Sur; Virginia Jan, Hospital de Especialidades Vida Mejor; Victor Hugo Garzon Barrientos, Hospital General de Chilpancingo; Pablo Ruiz Flores, Universidad Autonoma de Coahuila; Perla Karina Espino Silva, Universidad Autonoma de Coahuila; Jorge Haro Santa Cruz, Universidad Autonoma de Coahuila; Hector Martinez Gregorio, Facultad de Estudios Superiores Iztacala; Ernesto Arturo Rojas Jimenez, Facultad de Estudios Superiores Iztacala; Luis Enrique Romero Cruz, Facultad de Estudios Superiores Iztacala; Claudia Fabiola Mendez Catala, Facultad de Estudios Superiores Iztacala; Rosa Maria Alvarez Gomez, Instituto Nacional de Cancerologia; Veronica Fragoso Ontiveros, Instituto Nacional de Cancerologia; Luis Alonso Herrera, Instituto Nacional de Cancerologia; Isabelle Romieu, Emory University; Luis Ignacio Terrazas, Facultad de Estudios Superiores Iztacala; Yolanda Irasema Chirino, Facultad de Estudios Superiores Iztacala; Cecilia Frecha, Hospital Italiano Buenos Aires; Javier Oliver, Hospital Italiano Buenos Aires; Sandra Perdomo, Universidad El Bosque; Felipe Vaca Paniagua, Facultad de Estudios Superiores Iztacala
• Language: English
• Date: 2018-10-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2018 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/cancers10100361
• Title of Journal or Parent Work: Cancers
• ISSN: 2072-6694
• Volume: 10
• Issue: 10
• Grant/Funding Information: This work was supported by the National Autonomous University of Mexico (UNAM: PAPIIT IA204215) and by the National Council for Science and Technology (CONACyT: 285879, 264410, 271685). Rosalía Quezada-Urban received a scholarship from CONACyT and in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute.
• Keywords: gene panel; genetic screening; Life Sciences & Biomedicine; BRCA1/2; Oncology; PROSTATE-CANCER; MEDICAL GENETICS; AMERICAN-COLLEGE; EPISTATIC INTERACTION; RISK-ASSESSMENT; SEQUENCE VARIANTS; massive parallel sequencing; GENETIC-HETEROGENEITY; Science & Technology; BRCA2 MUTATION CARRIERS; pathogenic variants; hereditary breast cancer; IDENTIFIES MULTIPLE; MULTIGENE PANEL
• Research Categories: Health Sciences, Oncology

Abstract

Hereditary breast and ovarian cancer syndrome (HBOC) represents 5⁻10% of all patients with breast cancer and is associated with high-risk pathogenic alleles in BRCA1/2 genes, but only for 25% of cases. We aimed to find new pathogenic alleles in a panel of 143 cancer-predisposing genes in 300 Mexican cancer patients with suspicion of HBOC and 27 high-risk patients with a severe family history of cancer, using massive parallel sequencing. We found pathogenic variants in 23 genes, including BRCA1/2. In the group of cancer patients 15% (46/300) had a pathogenic variant; 11% (33/300) harbored variants with unknown clinical significance (VUS) and 74% (221/300) were negative. The high-risk group had 22% (6/27) of patients with pathogenic variants, 4% (1/27) had VUS and 74% (20/27) were negative. The most recurrent mutations were the Mexican founder deletion of exons 9-12 and the variant p.G228fs in BRCA1, each found in 5 of 17 patients with alterations in this gene. Rare VUS with potential impact at the protein level were found in 21 genes. Our results show for the first time in the Mexican population a higher contribution of pathogenic alleles in other susceptibility cancer genes (54%) than in BRCA1/2 (46%), highlighting the high locus heterogeneity of HBOC and the necessity of expanding genetic tests for this disease to include broader gene panels.