HNPCC: Six new pathogenic mutations

• Main Authors: Epplen Joerg T, Hahn Stephan A, Brasch Frank E, Vieland Judith, Kunstmann Erdmute, Schulmann Karsten, Schmiegel Wolff
• Format: Article
• Language: English
• Published: BMC 2004-06-01
• Series: BMC Medical Genetics
• Online Access: http://www.biomedcentral.com/1471-2350/5/16

<p>Abstract</p> <p>Background</p> <p>Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease with a high risk for colorectal and endometrial cancer caused by germline mutations in DNA mismatch-repair genes (MMR). HNPCC accounts for approximately 2 to 5% of all colorectal cancers. Here we present 6 novel mutations in the DNA mismatch-repair genes <it>MLH1</it>, <it>MSH2 </it>and <it>MSH6</it>.</p> <p>Methods</p> <p>Patients with clinical diagnosis of HNPCC were counselled. Tumor specimen were analysed for microsatellite instability and immunohistochemistry for MLH1, MSH2 and MSH6 protein was performed. If one of these proteins was not detectable in the tumor mutation analysis of the corresponding gene was carried out.</p> <p>Results</p> <p>We identified 6 frameshift mutations (2 in <it>MLH1</it>, 3 in <it>MSH2</it>, 1 in <it>MSH6</it>) resulting in a premature stop: two mutations in <it>MLH1 </it>(c.2198_2199insAACA [p.N733fsX745], c.2076_2077delTG [p.G693fsX702]), three mutations in <it>MSH2 </it>(c.810_811delGT [p.C271fsX282], c.763_766delAGTGinsTT [p.F255fsX282], c.873_876delGACT [p.L292fsX298]) and one mutation in <it>MSH6 </it>(c.1421_1422dupTG [p.C475fsX480]). All six tumors tested for microsatellite instability showed high levels of microsatellite instability (MSI-H).</p> <p>Conclusions</p> <p>HNPCC in families with <it>MSH6 </it>germline mutations may show an age of onset that is comparable to this of patients with <it>MLH1 </it>and <it>MSH2 </it>mutations.</p>