Amplification and overexpression of the KIT gene is associated with progression in the seminoma subtype of testicular germ cell tumors of adolescents and adults

Alan McIntyre, Brenda Summersgill, Beata Grygalewicz, Ad J. M. Gillis, J. Stoop, Ruud J. H. L. M. van Gurp, Nening Dennis, Cyril Fisher, Robert Huddart, Colin Cooper, Jeremy Clark, J. Wolter Oosterhuis, Leendert H. J. Looijenga, Janet Shipley

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Abstract

We have previously identified amplification at 4q12 in testicular germ cell tumors of adolescents and adults centered around the KIT gene encoding a tyrosine kinase transmembrane receptor. Analysis of primary testicular germ cell tumors totaling 190 cases revealed 21% of the seminoma subtype with an increased copy number of KIT whereas this change was rarely found in the nonseminomas. In most cases, gain of KIT did not include the immediately flanking noncoding DNA or the flanking genes KDR and PDGFRA. Increased copy number of KIT was not found in the putative precursor lesion, carcinoma in situ (CIS), adjacent to tumor with this change. KIT overexpression was found independent of gain and KIT immunostaining was stronger in selected cases with gain of KIT compared to those without. Taken together with activating mutations of KIT in exon 17 identified in 13% of seminomas, this suggests that the KIT gene product plays a role in the progression of CIS towards seminoma, the further understanding of which may lead to novel less toxic therapeutic approaches.
Original languageEnglish
Pages (from-to)8085-8089
Number of pages5
JournalCancer Research
Volume65
Issue number18
DOIs
Publication statusPublished - 15 Sep 2005

Keywords

  • Adolescent
  • Adult
  • Disease Progression
  • Gene Amplification
  • Gene Expression
  • Humans
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-kit
  • Receptor, Platelet-Derived Growth Factor alpha
  • Seminoma
  • Testicular Neoplasms
  • Vascular Endothelial Growth Factor Receptor-2

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