Germline Mutations in PALB2, BRCA1, and RAD51C, wich Regulate DNA Recombination Repair, in Patients with Gastric Cancer

ABSTRACT: Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2 , BRCA1 , or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer.

• Autores: González Castrillón, Luz María; Cock Rada, Alicia María; Bohorquez Lozano, Mabel Elena; Toa, Ted; Estrada Flórez, Ana Patricia; Suárez Olaya, John Jairo; Brea Fernández, Alejandro; Cameselle Teijeiro, José; Pinto, Carla; Ramos, Irma; Mantilla Morales, Alejandra; Prieto Sánchez, Rodrigo; Corvalán, Alejandro; Norero, Enrique; Álvarez, Carolina; Tapia, Teresa; Carvallo, Pilar; Sahasrabudhe, Ruta; Lott, Paul; Solano, Angela; Neffa, Florencia; Della Valle, Adriana; Yau, Chris; Soares, Gabriela; Borowsky, Alexander; Hu, Nan; He, Li-Ji; Han, Xiao-You; Taylor, Philip R.; Goldstein, Alisa M.; Torres, Javier; Echeverry De Polanco, María Magdalena; Ruiz Ponte, Clara; Rodrigues Teixeira, Manuel António; Carvajal Carmona, Luis Guillermo
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2017
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/34012
• Acceso en línea: https://hdl.handle.net/10495/34012
• Palabra clave: Stomach; Estómago; Stomach Neoplasms; Neoplasias Gástricas; Whole Exome Sequencing; Secuenciación del Exoma Completo; Fanconi Anemia Complementation Group N Protein; Proteína del Grupo de Complementación N de la Anemia de Fanconi; BRCA1 Protein; Proteína BRCA1; Recombinational DNA Repair; Reparación del ADN por Recombinación
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc-nd/2.5/co/