A Prognostic Signature of Defective P53-dependent G1 Checkpoint Function in Melanoma Cell Lines

Overview

Journal Pigment Cell Melanoma Res

Date 2012 May 1

PMID 22540896

Citations 17

Authors

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

Affiliations

Soon will be listed here.

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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