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The role of microsatellite instability in gastric carcinoma
  1. J D HAYDEN,
  1. Division of Surgery,
  2. University of Leeds, Leeds, UK
  3. Division of Molecular Oncology
  1. Dr Hayden, Division of Molecular Oncology, Algernon Firth Building, The University of Leeds, Leeds LS2 9JT, UK.

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During the past four years, the genetic basis of the hereditary non-polyposis colorectal cancer (HNPCC) syndrome has emerged.1 ,2 Most HNPCC carcinomas exhibit a mutator phenotype characterised by widespread alterations in the length of repetitive DNA sequences (that is, microsatellite instability). A defect in one or more of the known DNA mismatch repair genes results in the disruption of an enzyme system which maintains the integrity of repetitive sequences which are usually stably inherited.3Germline mutations in hMLH1, hMSH2, hPMS1, hPMS2, and possibly GTBP may account for over 90% of cases of HNPCC.4-8

A proportion of HNPCC kindreds (the so-called Lynch II families) are associated with a high frequency of extracolonic carcinomas, most commonly affecting the stomach and endometrium.9Endometrial and gastric carcinomas from HNPCC kindreds show evidence of microsatellite instability.10 The relation between microsatellite instability and gastric carcinoma has received considerable attention because of the suggestion that this mutator phenotype may also be found in sporadic carcinomas that are characteristic of the HNPCC syndrome.11 The implication is that there may be a group of sporadic gastric carcinomas which are either unrecognised HNPCC cases or a different biological subset of neoplasms, possibly requiring different clinical management.

The literature emerging from both the East and West concerning the role of microsatellite instability in gastric carcinoma is both conflicting and confusing. A number of factors have contributed to this, which include the diversity of populations studied, differences in the quantity and selection of microsatellite loci which are analysed, differences in the definition of a mutator phenotype used by various authors, and studies of small numbers of cases. It is essential to determine whether the detection of microsatellite instability in gastric carcinomas is clinically important or purely of academic interest.

Definitions and methods of detection

Microsatellites are ubiquitous short repetitive DNA …

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