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A genome-wide study of allelic imbalance in human testicular germ cell tumors using microsatellite markers

by Jon Thor Bergthorsson, Bjarni Agnar Agnarsson, Tomas Gudbjartsson, Kjartan Magnusson, Asgeir Thoroddsen, Birgir Palsson, Johannes Bjornsson, Kari Stefansson, Jeffrey Gulcher, Gudmundur Vikar Einarsson, Laufey Thora Amundadottir, Rosa Bjork Barkardottir show all authors
Cancer Genetics and Cytogenetics ()

Abstract

Testicular germ cell tumors (TGCT) arise by multistep carcinogenesis pathways involving selective losses and gains of chromosome material. To locate cancer genes underlying this selection, we performed a genome-wide study of allelic imbalance (AI) in 32 tumors, using 710 microsatellite markers. The highest prevalence of AI was found at 12p, in line with previous studies finding consistent gain of the region in TGCTs. High frequency of AI was also observed at chromosome arms 4p, 9q, 10p, 11q, 11p, 13q, 16q, 18p, and 22q. Within 39 candidate regions identified by mapping of smallest regions of overlap (SROs), the highest frequency of AI was at 12p11.21???p11.22 (62%), 12p12.1???p13.1 (53%), 12p13.1???p13.2 (53%), 11q14.1???q14.2 (53%), 11p13???p14.3 (47%), 9q21.13???q21.32 (47%), and 4p15.1???p15.2 (44%). Two genes known to be involved in cancer reside in these regions, ETV6 at 12p13.2 (TEL oncogene) and WT1 at 11p13. We also found a significant association (P = 0.02) between AI at 10q21.1???q22.2 and higher clinical stage. This study contributes to the ongoing search for genes involved in transformation of germ cells and provides a useful reference point to previous studies using cytogenetic techniques to map chromosome changes in TGCTs. ?? 2006 Elsevier Inc. All rights reserved.

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