Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors.
case_report · Level V
Where this comes from
- Record sourced from PubMed, PMID 29760383.
- Also identified by DOI 10.1038/s41467-018-04322-5 and PMC identifier 5951831.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Metastatic uveal melanoma is a deadly disease with no proven standard of care. Here we present a metastatic uveal melanoma patient with an exceptional high sensitivity to a PD-1 inhibitor associated with outlier CpG>TpG mutation burden, MBD4 germline deleterious mutation, and somatic MBD4 inactivation in the tumor. We identify additional tumors in The Cancer Genome Atlas (TCGA) cohorts with similar hypermutator profiles in patients carrying germline deleterious MBD4 mutations and somatic loss of heterozygosity. This MBD4-related hypermutator phenotype may explain unexpected responses to immune checkpoint inhibitors.
Medical subject headings
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents, Immunological
- Endodeoxyribonucleases
- Germ-Line Mutation
- Melanoma
- Programmed Cell Death 1 Receptor
- Uveal Neoplasms