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MLH1
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Interpretation 2242
Tier 3
MLH1
Variants
MLH1 V384D
Primary Sites
Brain
Tumor Types
Glioblastoma
Astrocytoma, NOS
Astrocytoma, Pilocytic
Astrocytoma, Diffusely Infiltrating
Interpretation

MLH1 is a component of the cellular DNA mismatch repair (MMR) machinery. The MLH1 V384D mutation has been associated with cancer risk in some tumor types. This variant encodes in a partially impaired protein with diminished interaction with PMS2 protein and reduced MMR activity in vitro. The MLH1 V384D variant has not been reported as a somatic mutation in glial brain tumors. This variant has an allele frequency of 4% in the East Asian population. Some studies have shown that patients carrying the MLH V384D variant have an increased risk of the development of microsatellite-instable as well as -stable colorectal cancer. MLH1 V384D variant has also been reported to be associated with primary resistance to EGFR-TKIs in patients with EGFR L858R-positive lung adenocarcinoma. Of note, this variant is reported as a benign germline variant in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/41632/). Clinical correlation is recommended.

Citations
  1. Ceccarelli M, et al. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma. Cell. 2016 Jan 28;164(3):550-63.
  2. Chiu CH, et al. MLH1 V384D polymorphism associates with poor response to EGFR tyrosine kinase inhibitors in patients with EGFR L858R-positive lung adenocarcinoma. Oncotarget 2015;6(10):8407-17
  3. Ohsawa T, et al. Colorectal cancer susceptibility associated with the hMLH1 V384D variant. Mol Med Rep 2009;2(6):887-91
  4. Peng HX, et al. Molecular analysis of MLH1 variants in Chinese sporadiccolorectal cancer patients. Genet Mol Res. 2016 Apr 26;15(2).
  5. ClinVar MLH1 V384D: https://www.ncbi.nlm.nih.gov/clinvar/variation/41632/
Last updated: 2018-04-25 15:38:14 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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