Amplification and overexpression of the KIT gene is associated with progression in the seminoma subtype of testicular germ cell tumors of adolescents and adults.
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.
McIntyre
Alan
A
Molecular Cytogenetics, Section of Molecular Carcinogenesis, The Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Summersgill
Brenda
B
Grygalewicz
Beata
B
Gillis
Ad J M
AJ
Stoop
J
J
van Gurp
Ruud J H L M
RJ
Dennis
Nening
N
Fisher
Cyril
C
Huddart
Robert
R
Cooper
Colin
C
Clark
Jeremy
J
Oosterhuis
J Wolter
JW
Looijenga
Leendert H J
LH
Shipley
Janet
J
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
D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D040301:Vascular Endothelial Growth Factor Receptor-2