Mechanisms of chromosomal instability in melanoma

摘要: A systems biology approach was applied to investigate the mechanisms of chromosomal instability in melanoma cell lines. Chromosomal quantified using array comparative genomic hybridization identify somatic copy number alterations (deletions and duplications). Primary human melanocytes displayed an average 8.5 per primarily representing known polymorphisms. Melanoma lines 25 131 cell, with 68, indicative instability. Copy included approximately equal numbers deletions duplications greater hemizygous (−1,+1) than homozygous (−2,+2). oncogenes, such as BRAF MITF, tumor suppressor genes, CDKN2A/B PTEN, were these alterations. Duplications functional there significant correlations between DNA mRNA expression for genes. Spectral karyotype analysis three confirmed extensive polyploidy, aneuploidy, deletions, duplications, chromosome rearrangements. Bioinformatic identified a signature gene that correlated but this provided no clues The failed generate (P = 0.105) prediction progression separate dataset. not elements damage response (DDR) radiosensitivity, nucleotide excision repair, DDR biomarkers γH2AX P-CHEK2, nor G1 or G2 checkpoint function. appears influence function it is simply explained by system DDR. Environ. Mol. Mutagen. 55:457–471, 2014. © 2014 Wiley Periodicals, Inc.