Germline <i>MSH2</i> and <i>MLH1</i> mutational spectrum in HNPCC families from Poland and the Baltic States

Abstract

Hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome) is an autosomal dominantly inherited syndrome predisposing to the early development of cancers of the colon, rectum, endometrium, small bowel, and urinary tract and accounts for ∼5% of all colon cancer cases.1 There are at least five genes involved in this cancer predisposition and they include MLH1 ,2 MSH2 ,3 MSH6 ,4 PMS2 , and PMS1 .5 Currently, more than 300 different mutations have been described in these genes which account for approximately 500 HNPCC kindreds from different parts of the world.6 MLH1 and MSH2 genes show abnormalities in more than 90% of HNPCC families with identified germline mutations7 (http://www.nfdht.nl). The majority of reported MLH1 and MSH2 mutations are dispersed throughout the 35 exons of these two genes. However, some changes are recurrent and are described as founder mutations in particular populations.8–11 In order to develop efficient DNA testing, it is important to describe the nature and frequency of mutations that are characteristic of particular ethnic groups. The MSH2 and MLH1 mutation spectrum has not been investigated in the eastern European region and therefore there is no knowledge about any recurrent mutations which may significantly aid in the mutation screening procedures for this region. Here, we describe the results of DNA/RNA based mutation sequencing of both the MSH2 and MLH1 genes in a series of HNPCC families from Poland (89 cases) and the Baltic States (12 cases). ### Patients A total of 101 unrelated patients affected by colorectal cancer or an HNPCC associated cancer (endometrium, small bowel, urinary tract) were from 17 families which fulfilled the Amsterdam II criteria12 and from 84 families matching our modified criteria of suspected HNPCC, one colorectal cancer patient with a first degree relative affected by an HNPCC associated cancer, …