title: Amplification and overexpression of the KIT gene is associated with progression in the seminoma subtype of testicular germ cell tumors of adolescents and adults.
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.
authors.affiliation: Molecular Cytogenetics, Section of Molecular Carcinogenesis, The Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: McIntyre
authors.forename: Brenda
authors.initials: B
authors.lastname: Summersgill
authors.forename: Beata
authors.initials: B
authors.lastname: Grygalewicz
authors.forename: Ad J M
authors.initials: AJ
authors.lastname: Gillis
authors.forename: J
authors.initials: J
authors.lastname: Stoop
authors.forename: Ruud J H L M
authors.initials: RJ
authors.lastname: van Gurp
authors.forename: Nening
authors.initials: N
authors.lastname: Dennis
authors.forename: Cyril
authors.initials: C
authors.lastname: Fisher
authors.forename: Robert
authors.initials: R
authors.lastname: Huddart
authors.forename: Colin
authors.initials: C
authors.lastname: Cooper
authors.forename: Jeremy
authors.initials: J
authors.lastname: Clark
authors.forename: J Wolter
authors.initials: JW
authors.lastname: Oosterhuis
authors.forename: Leendert H J
authors.initials: LH
authors.lastname: Looijenga
authors.forename: Janet
authors.initials: J
authors.lastname: Shipley
mesh_terms: D000293:Adolescent; D000328:Adult; D018450:Disease Progression; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000096:biosynthesis / Q000235:genetics; D018239:Seminoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D013736:Testicular Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D040301:Vascular Endothelial Growth Factor Receptor-2