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

Publication ,  Journal Article
Mithani, SK; Smith, IM; Califano, JA
Published in: Melanoma Res
August 2011

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.

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Published In

Melanoma Res

DOI

EISSN

1473-5636

Publication Date

August 2011

Volume

21

Issue

4

Start / End Page

298 / 307

Location

England

Related Subject Headings

  • Transfection
  • Skin Neoplasms
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Middle Aged
  • Melanoma
  • Male
  • Humans
  • Genomics
  • Genes, Tumor Suppressor
 

Citation

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Mithani, S. K., Smith, I. M., & Califano, J. A. (2011). Use of integrative epigenetic and cytogenetic analyses to identify novel tumor-suppressor genes in malignant melanoma. Melanoma Res, 21(4), 298–307. https://doi.org/10.1097/CMR.0b013e328344a003
Mithani, Suhail K., Ian M. Smith, and Joseph A. Califano. “Use of integrative epigenetic and cytogenetic analyses to identify novel tumor-suppressor genes in malignant melanoma.Melanoma Res 21, no. 4 (August 2011): 298–307. https://doi.org/10.1097/CMR.0b013e328344a003.
Mithani, Suhail K., et al. “Use of integrative epigenetic and cytogenetic analyses to identify novel tumor-suppressor genes in malignant melanoma.Melanoma Res, vol. 21, no. 4, Aug. 2011, pp. 298–307. Pubmed, doi:10.1097/CMR.0b013e328344a003.

Published In

Melanoma Res

DOI

EISSN

1473-5636

Publication Date

August 2011

Volume

21

Issue

4

Start / End Page

298 / 307

Location

England

Related Subject Headings

  • Transfection
  • Skin Neoplasms
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Middle Aged
  • Melanoma
  • Male
  • Humans
  • Genomics
  • Genes, Tumor Suppressor