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

J. T. Poirier, E. E. Gardner, N. Connis, A. L. Moreira, E. De Stanchina, C. L. Hann, C. M. Rudin

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)5869-5878
Number of pages10
JournalOncogene
Volume34
Issue number48
DOIs
StatePublished - Nov 26 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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