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

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

Published In Pigment Cell Melanoma Res, (2012 Jul)

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 (Pýýý0.007) 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.

PubMed ID: 22540896

MeSH Terms: No MeSH terms associated with this publication