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Amplification and Overexpression of the KIT Gene Is Associated with Progression in the Seminoma Subtype of Testicular Germ Cell Tumors of Adolescents and Adults

¹ Molecular Cytogenetics and ² Cell Transformation, Section of Molecular Carcinogenesis, and ³ Tissue Resource Laboratory, The Institute of Cancer Research; ⁴ Academic Department of Urology, The Royal Marsden National Health Service Trust and Institute of Cancer Research, Sutton, Surrey, United Kingdom; ⁵ Department of Pathology, Erasmus MC-University Medical Center Rotterdam, Daniel den Hoed Cancer Center, Josephine Nefkens Institute, Rotterdam, the Netherlands; and ⁶ Histopathology, The Royal Marsden National Health Service Trust, London, United Kingdom

Requests for reprints: Janet Shipley, Molecular Cytogenetics, Male Urological Cancer Research Centre, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom. Phone: 44-20-8722-4273; Fax: 44-20-8770-7290; E-mail: janet.shipley{at}icr.ac.uk.

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.

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