Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer

Ruta Sahasrabudhe, Paul Lott, Mabel Bohorquez, Ted Toal, Ana P. Estrada, John J. Suarez, Alejandro Brea-Fernández, José Cameselle-Teijeiro, Carla Pinto, Irma Ramos, Alejandra Mantilla, Rodrigo Prieto, Alejandro Corvalan, Enrique Norero, Carolina Alvarez, Teresa Tapia, Pilar Carvallo, Luz M. Gonzalez, Alicia Cock-Rada, Angela SolanoFlorencia Neffa, Adriana Della Valle, Chris Yau, Gabriela Soares, Alexander D Borowsky, Nan Hu, Li Ji He, Xiao You Han, Magdalena Echeverry, Mabel Bohorquez, Rodrigo Prieto, John Suarez, Gilbert Mateus, Maria Mercedes Bravo, Fernando Bolaños, Alejandro Vélez, Alejandro Corvalan, Pilar Carvallo, Javier Torres, Luis Carvajal-Carmona, Philip R. Taylor, Alisa M. Goldstein, Javier Torres, Magdalena Echeverry, Clara Ruiz-Ponte, Manuel R. Teixeira, Luis G. Carvajal-Carmona

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)983-986.e6
Issue number5
StatePublished - Apr 1 2017


  • Interaction
  • Stomach
  • Tumor
  • WES

ASJC Scopus subject areas

  • Gastroenterology


Dive into the research topics of 'Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer'. Together they form a unique fingerprint.

Cite this