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Sequence analysis of the protein kinase gene family in human testicular germ‐cell tumors of adolescents and adults
Author(s) -
Bignell Graham,
Smith Raffaella,
Hunter Chris,
Stephens Philip,
Davies Helen,
Greenman Chris,
Teague Jon,
Butler Adam,
Edkins Sarah,
Stevens Claire,
O'Meara Sarah,
Parker Adrian,
Avis Tim,
Barthorpe Syd,
Brackenbury Lisa,
Buck Gemma,
Clements Jody,
Cole Jennifer,
Dicks Ed,
Edwards Ken,
Forbes Simon,
Gorton Matthew,
Gray Kristian,
Halliday Kelly,
Harrison Rachel,
Hills Katy,
Hinton Jonathon,
Jones David,
Kosmidou Vivienne,
Laman Ross,
Lugg Richard,
Menzies Andrew,
Perry Janet,
Petty Robert,
Raine Keiran,
Shepherd Rebecca,
Small Alexandra,
Solomon Helen,
Stephens Yvonne,
Tofts Calli,
Varian Jennifer,
Webb Anthony,
West Sofie,
Widaa Sara,
Yates Andy,
Gillis Ad J. M.,
Stoop Hans J.,
van Gurp Ruud J. H. L. M.,
Oosterhuis J. Wolter,
Looijenga Leendert H. J.,
Futreal P. Andrew,
Wooster Richard,
Stratton Michael R.
Publication year - 2006
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20265
Subject(s) - biology , point mutation , genetics , gene , exon , mutation , comparative genomic hybridization , somatic cell , cancer research , microbiology and biotechnology , chromosome
Abstract The protein kinase gene family is the most frequently mutated in human cancer. Previous work has documented activating mutations in the KIT receptor tyrosine kinase in testicular germ‐cell tumors (TGCT). To investigate further the potential role of mutated protein kinases in the development of TGCT and to characterize the prevalence and patterns of point mutations in these tumors, we have sequenced the coding exons and splice junctions of the annotated protein kinase family of 518 genes in a series of seven seminomas and six nonseminomas. Our results show a remarkably low mutation frequency, with only a single somatic point mutation, a K277E mutation in the STK10 gene, being identified in a total of more than 15 megabases of sequence analyzed. Sequencing of STK10 in an additional 40 TGCTs revealed no further mutations. Comparative genomic hybridization and LOH analysis using SNP arrays demonstrated that the 13 TGCTs mutationally screened through the 518 protein kinase genes were uniformly aneuploid with consistent chromosomal gains on 12p, 8q, 7, and X and losses on 13q, 18q, 11q, and 4q. Our results do not provide evidence for a mutated protein kinase implicated in the development of TGCT other than KIT . Moreover, they demonstrate that the general prevalence of point mutations in TGCT is low, in contrast to the high frequency of copy number changes. © 2005 Wiley‐Liss, Inc.