%0 Journal Article
%T Mutation analysis of genes that control the G1/S cell cycle in melanoma: TP53, CDKN1A, CDKN2A, and CDKN2B
%A Jos¨¦ Soto
%A Carmen M Cabrera
%A Salvio Serrano
%A Miguel L¨®pez-Nevot
%J BMC Cancer
%D 2005
%I BioMed Central
%R 10.1186/1471-2407-5-36
%X We analysed 39 primary and metastatic melanomas and 9 melanoma cell lines by single-stranded conformational polymorphism (SSCP).The single-stranded technique showed heterozygous defects in the TP53 gene in 8 of 39 (20.5%) melanoma tumors: three new single point mutations in intronic sequences (introns 1 and 2) and exon 10, and three new single nucleotide polymorphisms located in introns 1 and 2 (C to T transition at position 11701 in intron 1; C insertion at position 11818 in intron 2; and C insertion at position 11875 in intron 2). One melanoma tumor exhibited two heterozygous alterations in the CDKN2A exon 1 one of which was novel (stop codon, and missense mutation). No defects were found in the remaining genes.These results suggest that these genes are involved in melanoma tumorigenesis, although they may be not the major targets. Other suppressor genes that may be informative of the mechanism of tumorigenesis in skin melanomas should be studied.The transition from phase G1 to S of the cell cycle is controlled by sequential activation of cyclin/Cdk complexes (Cyclin-dependent kinases) [1]. Active cyclin/Cdk complexes phosphorylate and inactivate members of the retinoblastoma protein (Rb) family, which are negative regulators of G1 and S-phase progression, leading to the induction of E2F-regulated gene expression and cell proliferation. Inhibitors of cyclin/Cdk complexes, by binding to these complexes, negatively regulate cell cycle progression [2].Two families of Cdk-inhibitors (CKI) control the actions mediated by cyclin/Cdk complexes. p21 (also called WAF1, and CDKN1A; MIM# 116899) [3] is the founding member of the Cip/Kip family of CKI, which also includes p27 [4] and p57 [5]. Another class of Cdk inhibitors, the so-called INK4 proteins (named for their ability to inhibit cdk4), specifically target the cyclin D-dependent kinases [6]. To date, four INK4 proteins have been identified: the founding member p16INK4a (CDKN2A; MIM# 600160) [7], and three other closel
%U http://www.biomedcentral.com/1471-2407/5/36