No evidence of a role for activating CDK2 mutations in melanoma

Walker, G. and Hayward, N. (2001) No evidence of a role for activating CDK2 mutations in melanoma. Melanoma Research, 11 4: 343-348. doi:10.1097/00008390-200108000-00004

Author Walker, G.
Hayward, N.
Title No evidence of a role for activating CDK2 mutations in melanoma
Journal name Melanoma Research   Check publisher's open access policy
ISSN 0960-8931
Publication date 2001
Sub-type Article (original research)
DOI 10.1097/00008390-200108000-00004
Volume 11
Issue 4
Start page 343
End page 348
Total pages 6
Place of publication Philadelphia, P.A., U.S.A.
Publisher Lippincott Williams & Wilkins
Collection year 2001
Language eng
Subject C1
321015 Oncology and Carcinogenesis
730108 Cancer and related disorders
1112 Oncology and Carcinogenesis
Abstract Inactivation of p16(INK4a) and/or activation of cyclin-dependent kinase-4 (CDK4) are strongly associated with both susceptibility and progression in melanoma. Activating CDK4 mutations prevent the binding and inhibition of CDK4 by p16(INK4a). A second, more indirect role for CDK4 is in late G(1), where It may sequester the inhibitors p27(KIP1) or p21(CIP1) away from CDK2, and in doing so upregulate the CDK2 activity necessary for cells to proceed completely through G(1) into S phase. As the pivotal residues around the most predominant R24C activating CDK4 mutation are invariant between CDK2 and CDK4, we speculated that the pivotal arginine (position 22 in CDK2), or a nearby residue, may be mutated in some melanomas, resulting in the diminution of its binding and inhibition by p27(KIP1) or p21(CIP1). However, except for a silent polymorphism, we detected no variants within this region of the CDK2 gene in 60 melanoma cell lines. Thus, if CDK2 activity is dysregulated in melanoma it is likely to occur by a means other than mutations causing loss of direct inhibition. We also examined the expression of the CDK2 gene in melanoma cell lines, to assess its possible co-regulation with the gene for the melanocyte-lineage antigen pmel17, which maps less than 1 kb away in head to head orientation with CDK2 and may be transcribed off the same bidirectional promoter. However, expression of the genes is not co-regulated. (C) 2001 Lippincott Williams & Wilkins.
Keyword Oncology
Medicine, Research & Experimental
Cell Cycle
Cutaneous Malignant-melanoma
Germline Mutations
Brca1 Gene
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 14 Aug 2007, 15:29:39 EST