Germline Loss-of-function Variants in MBD4 are Rare in Finnish Patients with Uveal Melanoma.

Germline Loss-of-function Variants in MBD4 are Rare in Finnish Patients with Uveal Melanoma. Pigment Cell Melanoma Res. 2020 May 18;: Authors: Repo P, Jäntti JE, Järvinen RS, Rantala ES, Täll M, Raivio V, Kivelä TT, Turunen JA Abstract Uveal melanoma (UM) is a rare intraocular cancer with the highest incidence in Northern latitudes. Metastases develop in approximately 50% of patients whereafter the median survival is 13 months. Generally, the mutation burden of these tumors is low. Germline variants predisposing to UM have been previously described in BRCA1 associated protein 1 (BAP1). Recently, germline and somatic loss-of-function (LOF) variants in the methyl-CpG binding domain-4 (MBD4) gene have been found to cause a hypermutated UM, and MBD4 also has been put forward as a gene predisposing to UM. We sequenced for MBD4 germline variants 440 Finnish patients with UM and identified seven rare exonic missense variants in 16 (3.6%) patients, of which one likely alters MBD4 function. The frequency of likely pathogenic variants in our cohort is 0.23% (1/432; 95% CI, 0.01-1.28). We identified no LOF variants though their frequency in the Finnish population is 0.052%. Thus, our data do not support the suggestion that MBD4 germline variants predispose to UM. Somatic loss of MBD4 might modify the mutational burden in UM and change its response to immune checkpoint inhibitors. PMID: 32421892 [PubMed - as supplied by publisher]
Source: Pigment Cell and Melanoma Research - Category: Cytology Authors: Tags: Pigment Cell Melanoma Res Source Type: research