Seven novel MLH1 and MSH2 germline mutations in hereditary nonpolyposis colorectal cancer |
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| Authors: | Stefan Krüger Jens Plaschke Steffen Pistorius Birgit Jeske Stephan Haas Heike Krämer Irene Hinterseher Andrea Bier Friedmar R Kreuz Franz Theissig Hans D Saeger Hans K Schackert |
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| Institution: | 1. Department of Surgical Research, Universit?tsklinikum Carl Gustav Carus, University of Technology, Dresden, GermanyDepartment of Surgical Research, Universit?tsklinikum Carl Gustav Carus, University of Technology, Fetscherstrasse 74, 01307 Dresden, Germany;2. Tel.: +49‐351‐4583873;3. Fax: +49‐351‐4585365;4. Department of Surgical Research, Universit?tsklinikum Carl Gustav Carus, University of Technology, Dresden, Germany;5. Department of Visceral, Thoracic and Vascular Surgery, Universit?tsklinikum Carl Gustav Carus, University of Technology, Dresden, Germany;6. Institute of Clinical Genetics, Universit?tsklinikum Carl Gustav Carus, University of Technology, Dresden, Germany;7. Department of Pathology, Universit?tsklinikum Carl Gustav Carus, University of Technology, Dresden, Germany |
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| Abstract: | Hereditary nonpolyposis colorectal cancer (HNPCC) is the most frequent hereditary form of colorectal cancer and is caused by germline mutations in mismatch repair (MMR) genes. The majority of mutations occur in MLH1 and MSH2. We report hereby seven novel germline mutations in these two genes (five in MLH1 and two in MSH2). All mutations have been found in families fulfilling criteria of the Bethesda guidelines and four of which also fulfilled the Amsterdam criteria. We identified three insertions or deletions of 1 bp leading to premature stop codons (MLH1: c.341delC, c.1413‐1414insA; MSH2: c.1119delG) and three nonsense mutations (MLH1: c.67G>T E23X], c.436C>T Q146X]; MSH2: c.1857T>G Y619X]). The corresponding tumors showed a high level of microsatellite instability (MSI‐H) and a complete loss of expression of the affected protein. In addition, a missense mutation in MLH1 was identified (c.1984A>C T662P]). The respective tumor also showed a high level of microsatellite instability but a reduced, rather then lost, expression of the MLH1‐protein. This missense mutation was not found in 107 healthy control individuals and in 54 HNPCC patients. © 2001 Wiley‐Liss, Inc. |
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| Keywords: | HNPCC mismatch repair MMR germline mutations microsatellite instability MSI protein expression MLH1 MSH2 |
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