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

Cancers

Isabelle Romieu¹  Pablo Ruiz Flores²  Perla Karina Espino Silva²  Jorge Haro Santa Cruz²  Fernando Rodríguez León³  Héctor Ochoa Díaz López³  Michael Dean⁴  María Patricia Rojo Castillo⁵  Rina Gitler⁵  Max Sirota Toporek⁵  Lizbeth García Esquivel⁵  Andrea Figueroa Morales⁵  Oscar Moreno García⁵  Víctor Hugo Garzón Barrientos⁶  Javier Oliver⁷  Cecilia Frecha⁷  Iván Delgado Enciso⁸  Rosa María Álvarez Gómez⁹  Verónica Fragoso Ontiveros⁹  Gabriela Torres Mejía^1,10  Virginia Jan^1,11  Sandra Perdomo^1,12  Rosalía Quezada Urban^1,13  Luis Ignacio Terrazas^1,13  Clara Estela Díaz Velásquez^1,13  Luis Enrique Romero Cruz^1,13  Felipe Vaca Paniagua^1,13  Claudia Fabiola Méndez Catalá^1,13  Yolanda Irasema Chirino^1,13  Héctor Martínez Gregorio^1,13  Ernesto Arturo Rojas Jiménez^1,13  Luis Alonso Herrera^1,14 

[1] Center for Center for Research on Population Health, National Institute of Public Health, Cuernavaca 62100, Morelos, Mexico;Centro de Investigación Biomédica, Universidad Autónoma de Coahuila, Torreón 27000, Coahuila, Mexico;Department of Health, El Colegio de la Frontera Sur (ECOSUR), San Cristóbal de Las Casas 29290, Chiapas, Mexico;Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA;Fundación Alma, CDMX 11560, Mexico;Hospital General de Chilpancingo, Chilpancingo de los Bravo 39019, Guerrero, Mexico;Hospital Italiano, Buenos Aires C1199ABB, Argentina;Instituto Estatal de Cancerología de Colima, Colima 28000, Colima, Mexico;Instituto Nacional de Cancerología, CDMX 14080, Mexico;Instituto Nacional de Salud Pública, 62100 Cuernavaca, Morelos, Mexico;Internal Medicine, Hospital de Especialidades Vida Mejor, ISSTECH, Tuxtla Gutiérrez 29040, Chiapas, Mexico;Investigación en Nutrición, Genética y Metabolismo, Facultad de Medicina, Universidad El Bosque, Bogotá 110121, Colombia;Laboratorio Nacional en Salud, Diagnóstico Molecular y Efecto Ambiental en Enfermedades Crónico-Degenerativas, Facultad de Estudios Superiores Iztacala, Tlalnepantla, Estado de México 54090, Mexico;Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas-Instituto Nacional de Cancerología, CDMX 14080, Mexico;

关键词: BRCA1/2;    genetic screening;    hereditary breast cancer;    massive parallel sequencing;    gene panel;    pathogenic variants;   

DOI  :  10.3390/cancers10100361

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown