Abstract
There is currently no effective treatment for metastasised uveal melanoma (UM). Recently, it was reported that a UM patient was responsive to checkpoint inhibitor (CI) treatment, due to a high tumour mutation burden correlated with a germline loss-of-function MBD4 mutation. Here, we report on another UM patient who carried an MBD4 germline nonsense variant (p.Leu563Ter) and her tumour showed a fivefold higher than average mutation burden. We confirmed the association between germline loss-of-function variant in MBD4 and CI response. The patient experienced stable disease (10 months) and survived 2 years with metastatic disease, which is twice as long as median survival. Additionally, the frequency of MBD4 loss-of-function variants in reported UM cohorts was > 20 times higher than in an aggregated population genome database (P < 5 × 10-5), implying a potential role as UM predisposition gene. These findings provide a strong basis for the inclusion of MBD4 in the screening of potential UM-prone families as well as stratification of immunotherapy.
Original language | English |
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Pages (from-to) | 433-436 |
Number of pages | 4 |
Journal | Immunogenetics |
Volume | 71 |
Issue number | 5-6 |
Early online date | 4 Feb 2019 |
DOIs | |
Publication status | Published - 1 May 2019 |
Keywords
- Immunotherapy
- MBD4
- Mutation
- Predisposition gene
- Uveal melanoma