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A prognostic signature of defective p53‐dependent G1 checkpoint function in melanoma cell lines
Author(s) -
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.
Publication year - 2012
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2012.01010.x
Subject(s) - melanoma , cancer research , g2 m dna damage checkpoint , cell cycle checkpoint , cell culture , transactivation , biology , cell cycle , cancer , gene expression , gene , genetics
Summary 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.