title: A prognostic signature of defective p53-dependent G1 checkpoint function in melanoma cell lines.
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.
authors.affiliation: Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Carson
authors.forename: Bernard
authors.initials: B
authors.lastname: Omolo
authors.forename: Haitao
authors.initials: H
authors.lastname: Chu
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Sambade
authors.forename: Eldon C
authors.initials: EC
authors.lastname: Peters
authors.forename: Patrick
authors.initials: P
authors.lastname: Tompkins
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Simpson
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Thomas
authors.forename: Cheng
authors.initials: C
authors.lastname: Fan
authors.forename: Alain
authors.initials: A
authors.lastname: Sarasin
authors.forename: Philippe
authors.initials: P
authors.lastname: Dessen
authors.forename: Janiel M
authors.initials: JM
authors.lastname: Shields
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Ibrahim
authors.forename: William K
authors.initials: WK
authors.lastname: Kaufmann
mesh_terms: D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D015342:DNA Probes / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012878:Skin Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015342:DNA Probes; D016159:Tumor Suppressor Protein p53