Article

Germline MSH2 and MLH1 mutational spectrum in HNPCC families from Poland and the Baltic States

Hereditary Cancer Centre, Department of Genetics and Pathology, Pomeranian Academy of Medicine, Szczecin, Poland.
Journal of Medical Genetics (Impact Factor: 5.64). 11/2002;
Source: PubMed Central
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    ABSTRACT: IntroductionThe aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes.Materials and methodsFrom 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH) examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis.ResultsFrom the 865 CRC cases only 3 (0.35%) pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) and 15 cases (1.73%) were suspected of HNPCC. In 69 cases (8%) with a cancer family aggregation (CFA) were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC) followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations.For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form.ConclusionsExisting pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.
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