MLH1 is a component of the cellular DNA mismatch repair (MMR) machinery causing hereditary nonpolyposis colorectal cancer (HNPCC), and is associated with specific somatic alterations in the tumor, characterized by high microsatellite instability (MSI-H). 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 in thyroid tumors. However, some other MLH1 variants have been described in some thyroid tumors, but their clinical significance is yet to be determined. Of note, according to one report, MLH1 V384D variant has been reported to be associated with primary resistance to EGFR-TKIs in patients with EGFR L858R-positive lung adenocarcinoma. Clinical correlation is recommended.
- Kunstman JW, et al. Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing. Hum Mol Genet 2015;24(8):2318-29
- 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
- Ohsawa T, et al. Colorectal cancer susceptibility associated with the hMLH1 V384D variant. Mol Med Rep 2009;2(6):887-91