ABSTRACTS UROLOGICAL ONCOLOGY: TESTIS CANCER AND ADVANCES IN ONCOLOGICAL THERAPY New Insights Into Testicular Germ Cell Tumorigenesis From Gene Expression Profiling

UROLOGICAL ONCOLOGY: TESTIS CANCER AND ADVANCES IN ONCOLOGICAL THERAPY New Insights Into Testicular Germ Cell Tumorigenesis From Gene Expression Profiling R. I. SKOTHEIM, O. MONNI, S. MOUSSES, S. D. FOSSA, O. P. KALLIONIEMI, R. A. LOTHE AND A. KALLIONIEMI, Department of Genetics, Institute for Cancer Research, and Department for Oncology and Radiotherapy, Norwegian Radium Hospital, Oslo, Norway, Biomedicum Biochip Center, Biomedicum Helsinki, Helsinki, and Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland, and Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland Cancer Res, 62: 2359–2364, 2002 We have shown recently that about half of the human TGCTs reveal DNA copy number increases affecting two distinct regions on chromosome arm 17q. To identify potential target genes with elevated expressions attributable to the extra copies, we constructed a cDNA microarray containing 636 genes and expressed sequence tags from chromosome 17. The expression patterns of 14 TGCTs, 1 carcinoma in situ, and 3 normal testis samples were examined, all with known chromosome 17 copy numbers. The growth factor receptor-bound protein 7 (GRB7) and junction plakoglobin (JUP) were the two most highly overexpressed genes in the TGCTs. GRB7 is tightly linked to ERBB2 and is coamplified and coexpressed with this gene in several cancer types. Interestingly, the expression levels of ERBB2 were not elevated in the TGCTs, suggesting that GRB7 might be the target for the increased DNA copy number in TGCTs. Because of the limited knowledge of altered gene expression in the development of TGCTs, we also examined the expression levels of 512 additional genes located throughout the genome. Several genes novel to testicular tumorigenesis were consistently upor down-regulated, including POV1, MYCL1, MYBL2, MXI1, and DNMT2. Additionally, overexpression of the proto-oncogenes CCND2 and MYCN were confirmed from the literature. The overexpressions were for some of the target genes closely associated to either seminoma or nonseminoma TGCTs, and hierarchical cluster analysis of the gene expression data effectively distinguished among the known histological subtypes. In summary, this focused functional genomic characterization of TGCTs has lead to the identification of new gene targets associated with a common genomic rearrangement as well as other genes with potential importance to testicular tumorigenesis. Editorial Comment: Chromosomal abnormalities have been identified in testicular germ cell tumors, especially isochromosome 12p. In addition, specific gains and losses from other chromosomal regions have been reported. The authors have built on their experience with comparative genomic hybridization to focus on overrepresentation of genes on chromosome 17q. They report use of a custom-made complementary DNA microarray with comprehensive chromosome 17 coverage. This study included 201 known genes from the entire chromosome 17. The authors identified 2 novel regions on chromosome 17q with common copy number increase. Interestingly the hierarchical cluster of complementary DNA microarray data segregated samples according to histological subtypes. This finding would suggest that some of the genes located on chromosome 17 may be important in the biological characteristics of these tumors. Also, when compared with comparative genomic hybridization, most of the genes that were over expressed because of extra DNA copies were not transcriptionally up-regulated. The likely candidate gene on chromosome 12p is CCND2. The POV1 gene at chromosome 11q was expressed in seminomas but not in nonseminomatous tumors. This technology has identified new candidate gene targets. The combination of comparative genomic hybridization with more sophisticated modified gene chip analysis is allowing the discovery of an ever more complex pattern of genes, some of which are clearly important in the development of testicular germ cell malignancy. Jerome P. Richie, M.D. Activated Status of Tumour-Infiltrating Lymphocytes and Apoptosis in Testicular Seminoma E. YAKIREVICH, O. LEFEL, Y. SOVA, A. STEIN, O. COHEN, O. BEN IZHAK AND M. B. RESNICK, Departments of Pathology, Surgery and Urology, Lady Davis Carmel Medical Center and Technion Rappaport Faculty of Medicine, and Department of Pathology, Rambam Medical Center, Haifa, Israel J Pathol, 196: 67–75, 2002 Permission to Publish Abstract Not Granted 0022-5347/02/1686-2722/0 Vol. 168, 2722–2743, December 2002 THE JOURNAL OF UROLOGY Printed in U.S.A. Copyright © 2002 by AMERICAN UROLOGICAL ASSOCIATION, INC. DOI: 10.1097/01.ju.0000035886.38127.14