2014年4月
Clarifying the impact of polycomb complex component disruption in human cancers
Molecular Cancer Research
- ,
- ,
- 巻
- 12
- 号
- 4
- 開始ページ
- 479
- 終了ページ
- 484
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1158/1541-7786.MCR-13-0596
- 出版者・発行元
- AMER ASSOC CANCER RESEARCH
The dysregulation of proper transcriptional control is a major cause of developmental diseases and cancers. Polycomb proteins form chromatin-modifying complexes that transcriptionally silence genome regions in higher eukaryotes. The BCL6 corepressor (BCOR) complex comprises ring finger protein 1B (RNF2/RING1B), polycomb group ring finger 1 (PCGF1), and lysine-specific demethylase 2B (KDM2B) and is uniquely recruited to nonmethylated CpG islands, where it removes histone H3K36me2 and induces repressive histone H2A monoubiquitylation. Germline BCOR mutations have been detected in patients with oculofaciocardiodental and Lenz microphthalmia syndromes, which are inherited conditions. Recently, several variants of BCOR and BCORlike 1 (BCORL1) chimeric fusion transcripts were reported in human cancers, including acute promyelocytic leukemia, bone sarcoma, and hepatocellular carcinoma. In addition, massively parallel sequencing has identified inactivating somatic BCOR and BCORL1 mutations in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia, medulloblastoma, and retinoblastoma. More importantly, patients with AML and MDS with BCOR mutations exhibit poor prognosis. This perspective highlights the detection of BCOR mutations and fusion transcripts of BCOR and BCORL1 and discusses their importance for diagnosing cancer subtypes and estimating the treatment responses of patients. Furthermore, this perspective proposes the need for additional functional studies to clarify the oncogenic mechanism by whichBCOR and BCORL1 are disrupted in cancers, and how this may lead to the development of novel therapeutics. Mol Cancer Res; 12(4); 479-84. © 2014 AACR.
- リンク情報
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- DOI
- https://doi.org/10.1158/1541-7786.MCR-13-0596
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/24515802
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000334583900001&DestApp=WOS_CPL
- 共同研究・競争的資金等の研究課題
- 急性前骨髄性白血病キメラ遺伝子BCOR-RARAによる白血病発症機序の解明
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84921999404&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84921999404&origin=inward
- ID情報
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- DOI : 10.1158/1541-7786.MCR-13-0596
- ISSN : 1541-7786
- eISSN : 1557-3125
- ORCIDのPut Code : 19003139
- PubMed ID : 24515802
- SCOPUS ID : 84921999404
- Web of Science ID : WOS:000334583900001