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Gastric carcinomas with microsatellite instability: clinical features and mutations to the TGF‐β type II receptor , IGFII receptor , and BAX genes
Author(s) -
Iacopetta Barry J.,
Soong Richie,
House Anthony K.,
Hamelin Richard
Publication year - 1999
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199903)187:4<428::aid-path264>3.0.co;2-a
Subject(s) - microsatellite instability , biology , frameshift mutation , gene , mutation , cancer research , epidermal growth factor receptor , phenotype , receptor , microsatellite , genetics , pathology , allele , medicine
Abstract The replication error phenotype (RER+) represents an important new form of genetic alteration characterized by widespread instability in repetitive nucleotide sequences. The aim of this study was to compare the features of RER+ gastric tumours with those of RER+ colonic tumours. RER status was determined by analysis of size alterations in the BAT‐26 mononucleotide repeat microsatellite. Twelve of 121 (10 per cent) gastric carcinomas from a low‐incidence region were found to be RER+. BAT‐26 instability was associated with tumours showing an absence of nodal invasion ( p = 0·009) and with a trend for improved prognosis. These tumours were more frequent in older, female patients. Frameshift mutations in mononucleotide repeat sequences within the transforming growth factor‐β receptor II (RII), insulin‐like growth factor II receptor (IGFIIR) , and BAX genes were observed in 83, 33, and 25 per cent, respectively, of RER+ tumours. Only 1/12 (8 per cent) RER+ tumours contained a p53 gene mutation compared with 29/109 (27 per cent) RER− tumours. RER+ gastric carcinomas therefore share several important features with RER+ colonic tumours, including less frequent nodal invasion, improved prognosis, a similar frequency of mutation in growth control genes containing repetitive nucleotide sequences, and a low frequency of mutation of the p53 tumour suppressor gene. Copyright © 1999 John Wiley & Sons, Ltd.