Open AccessMutational Analyses of Multiple Target Genes in Histologically Heterogeneous Gastric Cancer with Microsatellite Instability
Author(s) -
Wang Ying,
Shinmura Kazuya,
Guo RongJun,
Isogaki Jun,
Wang DongYu,
Kino Isamu,
Sugimura Haruhiko
Publication year - 1998
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1998.tb00525.x
Subject(s) - microsatellite instability , frameshift mutation , biology , cancer , mutation , gene , microsatellite , dna mismatch repair , cancer research , genetics , pathology , medicine , allele , colorectal cancer
It has been recognized that gastric cancer often shows histological heterogeneity in a single tumor. Although microsatellite instability (MSI) has been reported in gastric cancer, the significance of genomic instability in gastric cancers with histological heterogeneity within a single tumor has never been addressed. We investigated MSI at 8 microsatellite loci in 40 normal/tumor DNA pairs from 20 gastric cancers with histological heterogeneity. Six of 20 patients (10 DNAs of 40 tumor DNAs) had severe MSI in more than 3 loci. Four of the MSI‐positive cases had frameshift mutations in the poly(A) 10 tract of the TGFβRII gene. This mutation was found only in the MSI‐positive component in the 2 cases (cases 4 and 5) in which only 1 component exhibited MSI. The other 4 cases demonstrated homozygous or heteroclonal mutations (1 and 2 base deletions) in the poly(A) 8 tract of the hMSH3 gene; no mutation was detected in the poly(C) 8 tract of the hMSH6 gene in any of the MSI‐positive cases. The profile of alterations in multiple targets was different between the 2 components in most of the cases (5/6). These findings suggest that mismatch repair deficiency in MSI‐positive tumors causes multiple gene inactivations through frameshift mutations in short repetitive sequences in a heterogeneous way within a histologically heterogeneous tumor.