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Pigment Cell Melanoma Res. 2012 Jul;25(4):514-26. doi: 10.1111/j.1755-148X.2012.01010.x. Epub 2012 Jun 1.

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

Author information

1
Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

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.

PMID:
22540896
PMCID:
PMC3397470
DOI:
10.1111/j.1755-148X.2012.01010.x
[Indexed for MEDLINE]
Free PMC Article

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