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Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X.
Joseph, Nancy M; Chen, Yunn-Yi; Nasr, Anthony; Yeh, Iwei; Talevich, Eric; Onodera, Courtney; Bastian, Boris C; Rabban, Joseph T; Garg, Karuna; Zaloudek, Charles; Solomon, David A.
Afiliação
  • Joseph NM; Department of Pathology, University of California, San Francisco, CA, USA.
  • Chen YY; Clinical Cancer Genomics Laboratory, University of California, San Francisco, CA, USA.
  • Nasr A; Department of Pathology, University of California, San Francisco, CA, USA.
  • Yeh I; Pathology Sciences Medical Group, Chico, CA, USA.
  • Talevich E; Department of Pathology, University of California, San Francisco, CA, USA.
  • Onodera C; Clinical Cancer Genomics Laboratory, University of California, San Francisco, CA, USA.
  • Bastian BC; Clinical Cancer Genomics Laboratory, University of California, San Francisco, CA, USA.
  • Rabban JT; Clinical Cancer Genomics Laboratory, University of California, San Francisco, CA, USA.
  • Garg K; Department of Pathology, University of California, San Francisco, CA, USA.
  • Zaloudek C; Clinical Cancer Genomics Laboratory, University of California, San Francisco, CA, USA.
  • Solomon DA; Department of Pathology, University of California, San Francisco, CA, USA.
Mod Pathol ; 30(2): 246-254, 2017 02.
Article em En | MEDLINE | ID: mdl-27813512
ABSTRACT
Malignant mesothelioma is a rare cancer that arises from the mesothelial cells that line the pleural cavity and less commonly from the peritoneal lining of the abdomen and pelvis. Most pleural mesotheliomas arise in patients with a history of asbestos exposure, whereas the association of peritoneal mesotheliomas with exposure to asbestos and other potential carcinogens is less clear, suggesting that the genetic alterations that drive malignant peritoneal mesothelioma may be unique from those in pleural mesothelioma. Treatment options for all malignant mesotheliomas are currently limited, with no known targeted therapies available. To better understand the molecular pathogenesis of malignant peritoneal mesothelioma, we sequenced 510 cancer-related genes in 13 patients with malignant mesothelioma arising in the peritoneal cavity. The most frequent genetic alteration was biallelic inactivation of the BAP1 gene, which occurred in 9/13 cases, with an additional two cases demonstrating monoallelic loss of BAP1. All 11 of these cases demonstrated loss of BAP1 nuclear staining by immunohistochemistry, whereas two tumors without BAP1 alteration and all 42 cases of histologic mimics in peritoneum (8 multilocular peritoneal inclusion cyst, 6 well-differentiated papillary mesothelioma of the peritoneum, 16 adenomatoid tumor, and 12 low-grade serous carcinoma of the ovary) demonstrated intact BAP1 nuclear staining. Additional recurrently mutated genes in this cohort of malignant peritoneal mesotheliomas included NF2 (3/13), SETD2 (2/13), and DDX3X (2/13). While these genes are known to be recurrently mutated in pleural mesotheliomas, the frequencies are distinct in peritoneal mesotheliomas, with nearly 85% of peritoneal tumors harboring BAP1 alterations versus only 20-30% of pleural tumors. Together, these findings demonstrate the importance of epigenetic modifiers including BAP1, SETD2, and DDX3X in mesothelial tumorigenesis and suggest opportunities for targeted therapies.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Peritoneais / Histona-Lisina N-Metiltransferase / Proteínas Supressoras de Tumor / Ubiquitina Tiolesterase / Epigênese Genética / RNA Helicases DEAD-box / Neoplasias Pulmonares / Mesotelioma Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Peritoneais / Histona-Lisina N-Metiltransferase / Proteínas Supressoras de Tumor / Ubiquitina Tiolesterase / Epigênese Genética / RNA Helicases DEAD-box / Neoplasias Pulmonares / Mesotelioma Idioma: En Ano de publicação: 2017 Tipo de documento: Article