Use of integrative epigenetic and cytogenetic analyses to identify novel tumor-suppressor genes in malignant melanoma

Suhail K. Mithani, Ian M. Smith, Joseph A. Califano

Research output: Contribution to journalArticle

Abstract

The objective of this study was to identify novel tumor-suppressor genes in melanoma, using an integrative genomic approach. Data from: (i) earlier reports of DNA loss and gain in malignant melanoma accompanied by comparative genomic hybridization high-definition array data of the entire human genome; (ii) microarray expression data from melanoma-derived cell lines identifying genes with significantly increased expression due to methylation using a pharmacologic demethylating strategy; and (iii) publicly available RNA expression microarray data of primary tumors and benign nevi were integrated using statistical tools to define a population of candidate tumor-suppressor genes. Twenty-seven genes were identified in areas of deletion that demonstrated diminished expression in primary melanomas relative to benign nevi and were significantly increased in expression by 5-Aza treatment. Seven genes of these 27 genes demonstrated methylation and deletion in a validation cohort of 14 separate primary tumors. These were: CHRDL1, SFRP1, TMEM47, LPL, RARRES1, PLCXD1, and KOX15. All of these genes demonstrated growth-suppressive properties with transfection into melanoma-derived cell lines. Seven putative tumor-suppressor genes in malignant melanoma were identified using a novel integrative technique.

Original languageEnglish (US)
Pages (from-to)298-307
Number of pages10
JournalMelanoma Research
Volume21
Issue number4
DOIs
StatePublished - Aug 2011

Keywords

  • DNA hypermethylation
  • epigenetics
  • malignant melanoma
  • tumor suppressor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Dermatology

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