Hereditary predisposition in eye melanoma
Tuesday January 10, 2012
Study 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.
Source:
Abdel-Rahman MH, Pilarski R, Cebull CM, et al. Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers. J Med Genet 2011;48:856-859 doi:10.1136/jmedgenet-2011-100156
http://jmg.bmj.com/content/48/12/856.abstract?sid=a522d50c-b021-4e0b-9fa3-a71e5657cf15
See also Ohio State University media release:
http://cancer.osu.edu/mediaroom/releases/Pages/Ohio-State-Researchers-Discover-Hereditary-Predisposition-to-Melanoma-of-the-Eye.aspx
