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DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2.

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  • معلومة اضافية
    • المصدر:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5594 (Electronic) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE
    • بيانات النشر:
      Publication: <2002->: Basingstoke : Nature Publishing Group
      Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987-
    • الموضوع:
      DNA Methylation* ; Gene Expression Regulation, Neoplastic*; Biomarkers, Tumor/*analysis ; Lung Neoplasms/*classification ; Polycomb Repressive Complex 2/*genetics ; Polycomb Repressive Complex 2/*metabolism ; Small Cell Lung Carcinoma/*classification; Animals ; Blotting, Western ; CpG Islands ; Enhancer of Zeste Homolog 2 Protein ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Mice ; Polycomb Repressive Complex 2/antagonists & inhibitors ; Promoter Regions, Genetic ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Small Cell Lung Carcinoma/genetics ; Small Cell Lung Carcinoma/metabolism ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays
    • نبذة مختصرة :
      Small cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastasis, rapid development of resistance to chemotherapy and genetic instability. This study profiles DNA methylation in SCLC, patient-derived xenografts (PDX) and cell lines at single-nucleotide resolution. DNA methylation patterns of primary samples are distinct from those of cell lines, whereas PDX maintain a pattern closely consistent with primary samples. Clustering of DNA methylation and gene expression of primary SCLC revealed distinct disease subtypes among histologically indistinguishable primary patient samples with similar genetic alterations. SCLC is notable for dense clustering of high-level methylation in discrete promoter CpG islands, in a pattern clearly distinct from other lung cancers and strongly correlated with high expression of the E2F target and histone methyltransferase gene EZH2. Pharmacologic inhibition of EZH2 in a SCLC PDX markedly inhibited tumor growth.
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    • Grant Information:
      P30 CA008748 United States CA NCI NIH HHS
    • الرقم المعرف:
      0 (Biomarkers, Tumor)
      0 (RNA, Messenger)
      EC 2.1.1.43 (EZH2 protein, human)
      EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
      EC 2.1.1.43 (Polycomb Repressive Complex 2)
    • الموضوع:
      Date Created: 20150310 Date Completed: 20160308 Latest Revision: 20181113
    • الموضوع:
      20240829
    • الرقم المعرف:
      PMC4564363
    • الرقم المعرف:
      10.1038/onc.2015.38
    • الرقم المعرف:
      25746006