Sequence analysis of the protein kinase gene family in human testicular germ-cell tumors of adolescents and adults

Graham Bignell, Raffaella Smith, Chris Hunter, Philip Stephens, Helen Davies, Chris Greenman, Jon Teague, Adam Butler, Sarah Edkins, Claire Stevens, Sarah O'Meara, Adrian Parker, Tim Avis, Syd Barthorpe, Lisa Brackenbury, Gemma Buck, Jody Clements, Jennifer Cole, Ed Dicks, Ken EdwardsSimon Forbes, Matthew Gorton, Kristian Gray, Kelly Halliday, Rachel Harrison, Katy Hills, Jonathon Hinton, David Jones, Vivienne Kosmidou, Ross Laman, Richard Lugg, Andrew Menzies, Janet Perry, Robert Petty, Keiran Raine, Rebecca Shepherd, Alexandra Small, Helen Solomon, Yvonne Stephens, Calli Tofts, Jennifer Varian, Anthony Webb, Sofie West, Sara Widaa, Andy Yates, Ad J M Gillis, Hans J Stoop, Ruud J H L M van Gurp, J Wolter Oosterhuis, Leendert H J Looijenga, P Andrew Futreal, Richard Wooster, Michael R Stratton

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)42-6
Number of pages5
JournalGenes Chromosomes and Cancer
Volume45
Issue number1
DOIs
Publication statusPublished - Jan 2006
Externally publishedYes

Keywords

  • Adolescent
  • Adult
  • Chromosome Aberrations
  • Exons
  • Gene Dosage
  • Humans
  • Male
  • Middle Aged
  • Neoplasms, Germ Cell and Embryonal/genetics
  • Point Mutation
  • Protein Kinases/genetics
  • Protein Serine-Threonine Kinases/genetics
  • Seminoma/genetics
  • Testicular Neoplasms/genetics

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