Nature Genetics
8, 22 - 26 (1994)
doi:10.1038/ng0994-22
Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locusA. Kamb1, 9, D. Shattuck-Eidens1, R. Eeles2, 3, Q. Liu1, N. A. Gruis1, 4, W. Ding1, C. Hussey1, T. Tran1, Y. Miki2, J. Weaver-Feldhaus1, M. McClure1, J. F. Aitken5, D. E. Anderson6, W. Bergman4, R. Frants4, D. E. Goldgar2, A. Green5, R. MacLennan5, N. G. Martin5, L. J. Meyer7, 8, P. Youl5, J. J. Zone7, M. H. Skolnick1, 2
& L. A. Cannon-Albright7
1Myriad Genetics, Inc., 421 Wakara Way, Salt Lake City, Utah 84108, USA
2Department of Medical Informatics, University of Utah Medical Center, Salt Lake City, Utah 84108, USA
3CRC Academic Unit of Radiotherapy, Royal Marsden Hospital and Institute for Cancer Research, Sutton, Surrey, SM2 5PT, UK
4MGC-Department of Human Genetics and Department of Dermatology, Leiden University, Leiden, The Netherlands
5Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia
6Department of Molecular Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA
7Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA
8Geriatric Research Education and Clinical Center, Veteran's Administration Medical Center, Salt Lake City, Utah 84148, USA
9Correspondence should be addressed to A.K. A locus for familial melanoma, MLM, has been mapped within the same interval on chromosome 9p21 as the gene for a putative cell cycle regulator, p16INK4 (CDKN2) MTS1. This gene is homozygously deleted from many tumour cell lines including melanomas, suggesting that CDKN2 is a good candidate for MLM. We have analysed CDKN2 coding sequences in pedigrees segregating 9p melanoma susceptibility and 38 other melanoma-prone families. In only two families were potential predisposing mutations identified. No evidence was found for heterozygous deletions of CDKN2 in the germline of melanoma-prone individuals. The low frequency of potential predisposing mutations detected suggests that either the majority of mutations fall outside the CDKN2 coding sequence or that CDKN2 is not MLM.
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