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The tumor suppressor BAP1 cooperates with BRAFV600E to promote tumor formation in cutaneous melanoma.
Webster, Joshua D; Pham, Trang H; Wu, Xiumin; Hughes, Nicolas W; Li, Zhongwu; Totpal, Klara; Lee, Ho-June; Calses, Philamer C; Chaurushiya, Mira S; Stawiski, Eric W; Modrusan, Zora; Chang, Matthew T; Tran, Christopher; Lee, Wyne P; Chalasani, Sreedevi; Hung, Jeffrey; Sharma, Neeraj; Chan, Sara; Hotzel, Kathy; Talevich, Eric; Shain, Alan; Xu, Mengshu; Lill, Jennie; Dixit, Vishva M; Bastian, Boris C; Dey, Anwesha.
Affiliation
  • Webster JD; Department of Pathology, Genentech, Inc., South San Francisco, California.
  • Pham TH; Department of Discovery Oncology, Genentech, Inc., South San Francisco, California.
  • Wu X; Department of Translational Immunology, Genentech, Inc., South San Francisco, California.
  • Hughes NW; Departments of Dermatology and Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
  • Li Z; Departments of Dermatology and Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
  • Totpal K; Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China.
  • Lee HJ; Department of Translational Oncology, Genentech, Inc., South San Francisco, California.
  • Calses PC; Department of Discovery Oncology, Genentech, Inc., South San Francisco, California.
  • Chaurushiya MS; Department of Discovery Oncology, Genentech, Inc., South San Francisco, California.
  • Stawiski EW; Department of Physiological Chemistry, Genentech, Inc., South San Francisco, California.
  • Modrusan Z; Department of Molecular Biology, Genentech, Inc., South San Francisco, California.
  • Chang MT; Department of Molecular Biology, Genentech, Inc., South San Francisco, California.
  • Tran C; Department of Bioinformatics, Genentech, Inc., South San Francisco, California.
  • Lee WP; Department of Discovery Oncology, Genentech, Inc., South San Francisco, California.
  • Chalasani S; Department of Translational Immunology, Genentech, Inc., South San Francisco, California.
  • Hung J; Department of Pathology, Genentech, Inc., South San Francisco, California.
  • Sharma N; Department of Pathology, Genentech, Inc., South San Francisco, California.
  • Chan S; Department of Pathology, Genentech, Inc., South San Francisco, California.
  • Hotzel K; Department of Pathology, Genentech, Inc., South San Francisco, California.
  • Talevich E; Department of Pathology, Genentech, Inc., South San Francisco, California.
  • Shain A; Departments of Dermatology and Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
  • Xu M; Departments of Dermatology and Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
  • Lill J; Departments of Dermatology and Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
  • Dixit VM; Department of Microchemistry, Proteomics and Lipidomics, Genentech, Inc., South San Francisco, California.
  • Bastian BC; Department of Physiological Chemistry, Genentech, Inc., South San Francisco, California.
  • Dey A; Departments of Dermatology and Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
Pigment Cell Melanoma Res ; 32(2): 269-279, 2019 03.
Article in En | MEDLINE | ID: mdl-30156010
ABSTRACT
The deubiquitinating enzyme BAP1 is mutated in a hereditary cancer syndrome with a high risk of mesothelioma and melanocytic tumors. Here, we show that Bap1 deletion in melanocytes cooperates with the constitutively active, oncogenic form of BRAF (BRAFV600E ) and UV to cause melanoma in mice, albeit at very low frequency. In addition, Bap1-null melanoma cells derived from mouse tumors are more aggressive and colonize and grow at distant sites more than their wild-type counterparts. Molecularly, Bap1-null melanoma cell lines have increased DNA damage measured by γH2aX and hyperubiquitination of histone H2a. Therapeutically, these Bap1-null tumors are completely responsive to BRAF- and MEK-targeted therapies. Therefore, BAP1 functions as a tumor suppressor and limits tumor progression in melanoma.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Skin Neoplasms / Tumor Suppressor Proteins / Ubiquitin Thiolesterase / Proto-Oncogene Proteins B-raf / Carcinogenesis / Melanoma / Mutation Limits: Animals Language: En Journal: Pigment Cell Melanoma Res Journal subject: NEOPLASIAS Year: 2019 Document type: Article
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Skin Neoplasms / Tumor Suppressor Proteins / Ubiquitin Thiolesterase / Proto-Oncogene Proteins B-raf / Carcinogenesis / Melanoma / Mutation Limits: Animals Language: En Journal: Pigment Cell Melanoma Res Journal subject: NEOPLASIAS Year: 2019 Document type: Article