Somatic Mutation of Genes in Gastric and Colonic Cancers.

Nucleotide-binding and leucine-rich repeat protein (NLRP) genes are involved in inflammasome formation that plays a role in inflammation/host defense and cell death. Both cell death and inflammation are crucial for cancer development, but the roles of NLRPs in cancer are partially known. In this study, we analyzed mononucleotide repeats in coding sequences of and and found 1, 1, 1 and 8 frameshift mutation (s) in gastric (GC) and colonic cancers (CRC), respectively. Five of the 32 high microsatellite instability (MSI-H) GCs (15.5%) and 6 of 113 MSI-H CRCs (5.5%) exhibited the frameshift mutations. There was no frameshift mutations in microsatellite stable (MSS) GCs and CRCs. We also discovered that 2 of 16 CRCs (12.5%) harbored intratumoral heterogeneity (ITH) of the frameshift mutations in one or more areas. In both GC and CRC with MSI-H, NLRP9 expression in -mutated cases was significantly lower than that in -non-mutated cases. Our data indicate that is altered at multiple levels (frameshift mutation, mutational ITH and loss of expression), which together could contribute to pathogenesis of MSI-H GC and CRC.