Abstract
We examined 26 gastric carcinomas from British patients for mutations of the APC gene using a single-strand conformation polymorphism (SSCP) and heteroduplex assay in conjunction with the protein truncation test (PTT). In addition, we performed loss of heterozygosity (LOH) analysis of the APC and MCC genes. We detected an inactivating somatic mutation in one gastric tumour. LOH of APC was observed in one of 12 informative cases (8%) and of MCC in two of 20 cases (10%). We thus find that alteration of the APC and MCC genes are infrequent in gastric cancers from the British population. Tumour-suppressor genes on other chromosomes must play a more significant role in the development of these tumours.
Highlights
We analysed over 40% of the coding region of the APC gene
Subsequent sequencing revealed that we had detected a 4 bp deletion of either AGAG or GAGA in the sequence GAAAAGAGAGAGAGT at codon 14621465 (Figure lb). This mutation was located within the mutations in colorectal tumours are clustered (MCR)
The deletion was predicted to lead to truncation of the protein product due to the formation of an early stop codon
Summary
Twenty-six gastric cancers with corresponding normal stomach mucosa were obtained from seven hospitals in London. Twenty-two of the patients were UK residents, three were from the Middle East and one patient was from Brazil. Tissue samples were flash frozen in liquid nitrogen and kept at -70°C until use. The tumours were classified according to Lauren (1965) : 17 were of the intestinal histological type and nine of the diffuse type. DNA was extracted using the Nucleon II DNA extraction kit (Scotlab). Tumour samples used consisted of more than 50% neoplastic cells
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