Cancers, Vol. 10, Pages 361: Comprehensive Analysis of Germline Variants in Mexican Patients with Hereditary Breast and Ovarian Cancer Susceptibility

Cancers, Vol. 10, Pages 361: Comprehensive Analysis of Germline Variants in Mexican Patients with Hereditary Breast and Ovarian Cancer Susceptibility

Cancers doi: 10.3390/cancers10100361

Authors: Rosalía Quezada Urban Clara Díaz Velásquez Rina Gitler María Rojo Castillo Max Sirota Toporek Andrea Figueroa Morales Oscar Moreno García Lizbeth García Esquivel Gabriela Torres Mejía Michael Dean Iván Delgado Enciso Héctor Ochoa Díaz López Fernando Rodríguez León Virginia Jan Víctor Garzón Barrientos Pablo Ruiz Flores Perla Espino Silva Jorge Haro Santa Cruz Héctor Martínez Gregorio Ernesto Rojas Jiménez Luis Romero Cruz Claudia Méndez Catalá Rosa Álvarez Gómez Verónica Fragoso Ontiveros Luis Herrera Isabelle Romieu Luis Terrazas Yolanda Chirino Cecilia Frecha Javier Oliver Sandra Perdomo Felipe Vaca Paniagua

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.

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