Biochemical characterization of MLH3 missense mutations does not reveal an apparent role of MLH3 in Lynch syndrome
Copyright policy )Biochemical characterization of MLH3 missense mutations does not reveal an apparent role of MLH3 in Lynch syndrome
AbstractSo far 18 MLH3 germline mutations/variants have been identified in familial colorectal cancer cases. Sixteen of these variants are amino acid substitutions of which the pathogenic nature is still unclear. These substitutions are known as unclassified variants or UVs. To clarify a possible role for eight of these MLH3 UVs identified in suspected Lynch syndrome patients, we performed several biochemical tests. We determined the protein expression and stability, protein localization and interaction of the mutant MLH3 proteins with wildtype MLH1. All eight MLH3 UVs gave protein expression levels comparable with wildtype MLH3. Furthermore, the UV‐containing proteins, in contrast to previous studies, were all localized normally in the nucleus and they interacted normally with wildtype MLH1. Our different biochemical assays yielded no evidence that the eight MLH3 UVs tested are the cause of hereditary colorectal cancer, including Lynch syndrome. © 2009 Wiley‐Liss, Inc.
- University of Copenhagen Denmark
- University of Groningen Netherlands
- University of Copenhagen Denmark
- Copenhagen University Hospital Denmark
- University Medical Center Groningen Netherlands
EXPRESSION, MICROSATELLITE INSTABILITY, DNA Mutational Analysis, Molecular Sequence Data, Mutation, Missense, INTERACTS, Cell Line, SACCHAROMYCES-CEREVISIAE, Two-Hybrid System Techniques, Humans, Computer Simulation, Amino Acid Sequence, Adaptor Proteins, Signal Transducing, HMLH3, IDENTIFICATION, Nuclear Proteins, NONPOLYPOSIS COLORECTAL-CANCER, DNA MISMATCH REPAIR, GENE, Colorectal Neoplasms, Hereditary Nonpolyposis, PREDISPOSITION, Protein Transport, MutL Proteins, Carrier Proteins, MutL Protein Homolog 1, Sequence Alignment
EXPRESSION, MICROSATELLITE INSTABILITY, DNA Mutational Analysis, Molecular Sequence Data, Mutation, Missense, INTERACTS, Cell Line, SACCHAROMYCES-CEREVISIAE, Two-Hybrid System Techniques, Humans, Computer Simulation, Amino Acid Sequence, Adaptor Proteins, Signal Transducing, HMLH3, IDENTIFICATION, Nuclear Proteins, NONPOLYPOSIS COLORECTAL-CANCER, DNA MISMATCH REPAIR, GENE, Colorectal Neoplasms, Hereditary Nonpolyposis, PREDISPOSITION, Protein Transport, MutL Proteins, Carrier Proteins, MutL Protein Homolog 1, Sequence Alignment
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