Germline loss‐of‐function variants in MBD4 are rare in Finnish patients with uveal melanoma
| Autor: | Joni A. Turunen, Tero Kivelä, Johannes E. Jäntti, Virpi Raivio, Reetta-Stiina Järvinen, Elina S. Rantala, Martin Täll, Pauliina Repo |
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| Rok vydání: | 2020 |
| Předmět: |
Uveal Neoplasms
0301 basic medicine Somatic cell Dermatology medicine.disease_cause General Biochemistry Genetics and Molecular Biology Germline 03 medical and health sciences 0302 clinical medicine Loss of Function Mutation medicine Humans Missense mutation Melanoma Finland Germ-Line Mutation Loss function Aged BAP1 Mutation Endodeoxyribonucleases business.industry Cancer medicine.disease 3. Good health 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research business |
| Zdroj: | Pigment Cell & Melanoma Research. 33:756-762 |
| ISSN: | 1755-148X 1755-1471 |
| Popis: | 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 in 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. |
| Databáze: | OpenAIRE |
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