A prognostic signature of defective p53-dependent G1 checkpoint function in melanoma cell lines |
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Authors: | Carson Craig Omolo Bernard Chu Haitao Zhou Yingchun Sambade Maria J Peters Eldon C Tompkins Patrick Simpson Dennis A Thomas Nancy E Fan Cheng Sarasin Alain Dessen Philippe Shields Janiel M Ibrahim Joseph G Kaufmann William K |
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Affiliation: | Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. |
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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. |
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Keywords: | gene expression signature p53 function checkpoint melanoma |
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