Widespread microsatellite instability occurs infrequently in adenocarcinoma of the gastric cardia.
Heredity non-polyposis colorectal cancer (HNPCC) is associated with an increased predisposition to colorectal cancer and extra-colonic cancers of the gastro-intestinal, urological and female reproductive tracts. These tumours are characterised by an underlying defect in DNA mismatch repair and exhibit numerous replication errors throughout the genome (RER+ phenotype). HNPCC-associated gastric tumours, and a subset of sporadic, distally-located gastric tumours exhibit this RER+ phenotype. It is recognised that proximal and distal gastric tumours exhibit distinct epidemiological features. In this study we investigated the occurrence of microsatellite instability in a series of 38 primary gastric adenocarcinomas, arising in the proximal stomach. A total of 138 microsatellite markers, comprising mainly dinucleotide and tetranucleotide repeat units and covering all autosomal arms, excluding acrocentric arms, were analysed. One tumour demonstrated somatic microsatellite alterations at 62% (26 of 42) of loci tested. A further 32 tumours demonstrated levels of microsatellite instability ranging from 0.8% (1 of 28)-11.4% (15 of 132) of loci tested. Five tumours demonstrated no microsatellite alterations at any of the loci tested. These findings suggest that a high percentage of proximal gastric carcinomas exhibit a low level of microsatellite alterations at dinucleotide and tetranucleotide repeat loci. However, ubiquitous somatic alterations at these loci, characteristic of HNPCC-associated tumours, occur in a relatively small proportion of tumours.
Gleeson
C M
CM
Department of Medical Genetics, Queen's University of Belfast, Belfast City Hospital, N. Ireland.
Sloan
J M
JM
McGuigan
J A
JA
Ritchie
A J
AJ
Weber
J L
JL
Russell
S E
SE
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D002299:Cardia; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D004276:DNA, Satellite; D018900:Dinucleotide Repeats; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D007621:Karyotyping; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010641:Phenotype; D013274:Stomach Neoplasms / Q000235:genetics*
D004276:DNA, Satellite; D005819:Genetic Markers