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

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• 作者：Kevin J. McDonnell^a ; Gregory T. Gallanis^a ; Kathleen A. Heller^a ; Marilena Melas^a ; Gregory E. Idos^a ; Julie O. Culver^a ; Sue-Ellen Martin^a ; ^b ; David H. Peng^a ; ^c ; Stephen B. Gruber^a ; ^{sgruber@med.usc.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cancer genetics ; BAP1 ; tumor predisposition syndrome ; thyroid cancer ; melanoma
• 刊名：Cancer Genetics
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：209
• 期：3
• 页码：75-81
• 全文大小：1616 K

文摘

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.