Artículos de revistas
Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer
Fecha
2017-04Registro en:
Sahasrabudhe, Ruta; Lott, Paul; Bohorquez, Mabel; Toal, Ted; Estrada, Ana P.; et al.; Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer; W B Saunders Co-Elsevier Inc; Gastroenterology; 152; 5; 4-2017; 983-986
0016-5085
CONICET Digital
CONICET
Autor
Sahasrabudhe, Ruta
Lott, Paul
Bohorquez, Mabel
Toal, Ted
Estrada, Ana P.
Suarez, John J.
Brea Fernández, Alejandro
Cameselle Teijeiro, José
Pinto, Carla
Ramos, Irma
Mantilla, Alejandra
Prieto, Rodrigo
Corvalan, Alejandro
Norero, Enrique
Alvarez, Carolina
Tapia, Teresa
Carvallo, Pilar
Gonzalez, Luz M.
Cock-Rada, Alicia
Solano, Angela Rosario
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, Magdalena
Ruiz-Ponte, Clara
Teixeira, Manuel R.
Carvajal Carmona, Luis G.
Resumen
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.