A novel BAP1 mutation is associated with melanocytic neoplasms and thyroid cancer

• Published in: Cancer genetics Vol. 209; no. 3; pp. 75 - 81
• Main Authors: McDonnell, Kevin J, Gallanis, Gregory T, Heller, Kathleen A, Melas, Marilena, Idos, Gregory E, Culver, Julie O, Martin, Sue-Ellen, Peng, David H, Gruber, Stephen B
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2016
• Subjects: BAP1; Cancer genetics; Female; Germ-Line Mutation; Hematology, Oncology and Palliative Medicine; Humans; Medical Education; melanoma; Middle Aged; Nevus, Pigmented - genetics; Skin Neoplasms - genetics; thyroid cancer; Thyroid Neoplasms - genetics; tumor predisposition syndrome; Tumor Suppressor Proteins - analysis; Tumor Suppressor Proteins - genetics; Ubiquitin Thiolesterase - analysis; Ubiquitin Thiolesterase - genetics; Cancer genetics; melanoma; thyroid cancer; tumor predisposition syndrome; BAP1
• ISSN: 2210-7762; 2210-7770
• DOI: 10.1016/j.cancergen.2015.12.007

Germline mutations in the tumor suppressor gene, BRCA-1 associated protein ( BAP1 ), underlie a tumor predisposition syndrome characterized by increased risk for numerous cancers including uveal melanoma, melanocytic tumors and mesothelioma, among others. In the present study we report the identification of a novel germline BAP1 mutation, c.1777C>T, which produces a truncated BAP1 protein product and segregates with cancer. Family members with this mutation demonstrated a primary clinical phenotype of autosomal dominant, early-onset melanocytic neoplasms with immunohistochemistry (IHC) of these tumors demonstrating lack of BAP1 protein expression. In addition, family members harboring the BAP1 c.1777C>T germline mutation developed other neoplastic disease including thyroid cancer. IHC analysis of the thyroid cancer, as well, demonstrated loss of BAP1 protein expression. Our investigation identifies a new BAP1 mutation, further highlights the relevance of BAP1 as a clinically important tumor suppressor gene, and broadens the range of cancers associated with BAP1 inactivation. Further study will be required to understand the full scope of BAP1 -associated neoplastic disease.