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

   


Authors: Poirier, J. T.; Gardner, E. E.; Connis, N.; Moreira, A. L.; de Stanchina, E.; Hann, C. L.; Rudin, C. M.
Article Title: DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2
Abstract: 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. © 2015 Macmillan Publishers Limited All rights reserved.
Keywords: controlled study; protein expression; gene mutation; promoter region; single nucleotide polymorphism; nonhuman; animal cell; mouse; animal tissue; cell viability; protein bcl 2; gene expression; tumor volume; animal experiment; animal model; in vivo study; cell differentiation; tumor xenograft; protein p53; dna methylation; correlation analysis; epigenetics; cpg island; histone h3; upregulation; tumor growth; ex vivo study; loss of function mutation; small cell lung cancer; transcription initiation site; demethylation; transcription factor ezh2; histone methylation; transcription factor mash1; female; priority journal; article; lung cancer cell line; neurogenic differentiation factor; tazemetostat
Journal Title: Oncogene
Volume: 34
Issue: 48
ISSN: 0950-9232
Publisher: Nature Publishing Group  
Date Published: 2015-11-26
Start Page: 5869
End Page: 5878
Language: English
DOI: 10.1038/onc.2015.38
PROVIDER: scopus
PMCID: PMC4564363
PUBMED: 25746006
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84948570001&partnerID=40&md5=7e5351fb05e40600d09f0efd207cb8a2
Notes: Article -- 3 -- Export Date: 7 January 2016 -- 5869 -- Source: Scopus
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MSK Authors
  1. Andre L Moreira
    176 Moreira
  2. Elisa De Stanchina
    345 De Stanchina
  3. Charles Rudin
    489 Rudin
  4. John Thomas Poirier
    82 Poirier
  5. Eric Edison Gardner
    14 Gardner
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