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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. |
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List of authors: | McIntyre A; Summersgill B; Grygalewicz B; Gillis AJM; Stoop J; van Gurp RJHLM; Dennis N; Fisher C; Huddart R; Cooper CS; Clark J; Oosterhuis W; Looijenga LHJ; Shipley J. |
Reference: | Cancer Research, 65: 8085-8089 |
Year of Publication: | 2005 |
ISSN: | 0008-5472 |
Keywords: | KIT; testicular germ cell tumours |
Abstract: | We have previously identified amplification at 4q12 in testicular germ cell tumors of adolescents and adults (TGCTs) centered around the threonine kinase transmembrane receptor KIT. Analysis of two independent series of primary TGCTs totalling 190 cases revealed 22/107 seminomas with an increased copy number of KIT whilst this change was rarely found in non-seminomas. Gain of KIT included the flanking genes KDR and PDGFRA in 2/32 seminomas but significantly did not in 10/32 cases. Consistent with this, 10/75 of seminomas amplified KIT but not the immediately flanking non-coding DNA. Increased copy number of KIT was not found in the putative precursor lesion, carcinoma in situ, adjacent to tumor with this change. RNA overexpression was found independent of gain and KIT immuno-staining 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 4/32 seminomas this suggests that the KIT gene product plays a role in the progression of CIS towards seminomas the further understanding of which may lead to novel less toxic therapeutic approaches. |
PMID: | 16166280 |
Supplementary data: | KIT genomic copy number data (series 2) Primer and probe information for quantitative PCR and mutation screening CIS sample composition and corresponding KIT expression information |