Article Text
Abstract
Objective To investigate the potential contribution of germline sequence alterations in the BAP1 gene in uveal melanoma (UM) patients with possible predisposition to hereditary cancer.
Design A total of 53 unrelated UM patients with high risk for hereditary cancer and five additional family members of one proband were studied. Mutational screening was carried out by direct sequencing.
Results Of the 53 UM patients studied, a single patient was identified with a germline BAP1 truncating mutation, c. 799 C→T (p.Q267X), which segregated in several family members and was associated with UM and other cancers. Biallelic inactivation of BAP1 and decreased BAP1 expression were identified in the UM, lung adenocarcinoma and meningioma tumours from three family members with this germline BAP1 mutation. Germline BAP1 variants of uncertain significance, likely non-pathogenic, were also identified in two additional UM patients.
Conclusion This study reports a novel hereditary cancer syndrome caused by a germline BAP1 mutation that predisposes patients to UM, lung carcinoma, meningioma, and possibly other cancers. The results indicate that BAP1 is the candidate gene in only a small subset of hereditary UM, suggesting the contribution of other candidate genes.
- Uveal melanoma
- eye neoplasm
- familial cancer
- BAP1
- Cancer: hepatic
- Genetic screening/counselling
- molecular genetics
- ocular tumors
Statistics from Altmetric.com
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Files in this Data Supplement:
- Download Supplementary Data (PDF) - Manuscript file of format pdf
- Download Supplementary Data (PDF) - Manuscript file of format pdf
Footnotes
Funding This work is funded by the Patti Blow Research fund in Ophthalmology and by grant # IRG-67-003-47 from the American Cancer Society.
Competing interests None.
Ethics approval The Ohio State University Cancer Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.