A prognostic signature of defective p53-dependent G1 checkpoint function in melanoma cell lines

Craig Carson, Bernard Omolo, Haitao Chu, Yingchun Zhou, Maria J. Sambade, Eldon C. Peters, Patrick Tompkins, Dennis A. Simpson, Nancy E. Thomas, Cheng Fan, Alain Sarasin, Philippe Dessen, Janiel M. Shields, Joseph G. Ibrahim, William K. Kaufmann

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Melanoma cell lines and normal human melanocytes (NHM) were assayed for p53-dependent G1 checkpoint response to ionizing radiation (IR)-induced DNA damage. Sixty-six percent of melanoma cell lines displayed a defective G1 checkpoint. Checkpoint function was correlated with sensitivity to IR with checkpoint-defective lines being radio-resistant. Microarray analysis identified 316 probes whose expression was correlated with G1 checkpoint function in melanoma lines (P≤0.007) including p53 transactivation targets CDKN1A, DDB2, and RRM2B. The 316 probe list predicted G1 checkpoint function of the melanoma lines with 86% accuracy using a binary analysis and 91% accuracy using a continuous analysis. When applied to microarray data from primary melanomas, the 316 probe list was prognostic of 4-yr distant metastasis-free survival. Thus, p53 function, radio-sensitivity, and metastatic spread may be estimated in melanomas from a signature of gene expression.

Original languageEnglish (US)
Pages (from-to)514-526
Number of pages13
JournalPigment Cell and Melanoma Research
Volume25
Issue number4
DOIs
StatePublished - Jul 2012

Keywords

  • Checkpoint
  • Expression
  • Function
  • Gene
  • Melanoma
  • P53
  • Signature

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