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.
Asunto(s)
Proteína BRCA1/genética , Proteínas de Unión al ADN/genética , Proteínas Nucleares/genética , Neoplasias Gástricas/genética , Proteínas Supresoras de Tumor/genética , Anciano , Anciano de 80 o más Años , Proteína del Grupo de Complementación N de la Anemia de Fanconi , Femenino , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Humanos , Masculino , Persona de Mediana Edad , Mutación , Reparación del ADN por Recombinación/genéticaRESUMEN
We present the complete genome sequences of three Helicobacter pylori strains isolated from patients who resided in Tolima Department, Colombia, diagnosed with chronic gastritis. The genomes present an average length of 1.6 Mbp and 1,546 genes and correspond to different H. pylori subpopulations.