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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Mithani, SK; Smith, IM; Califano, JA

Published Date

  • August 2011

Published In

Volume / Issue

  • 21 / 4

Start / End Page

  • 298 - 307

PubMed ID

  • 21606880

Pubmed Central ID

  • 21606880

Electronic International Standard Serial Number (EISSN)

  • 1473-5636

International Standard Serial Number (ISSN)

  • 0960-8931

Digital Object Identifier (DOI)

  • 10.1097/CMR.0b013e328344a003

Language

  • eng