Expression profile of genes from 12p in testicular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2-p12.1

Rodriguez, S., Jafer, O., Goker, H., Summersgill, B. M., Zafarana, G., Gillis, A. J.M., Van Gurp, R. J.H.L.M., Oosterhuis, J. W., Lu, Y. J., Huddart, R., Cooper, C. S. ORCID:, Clark, J., Looijenga, L. H.J. and Shipley, J. M. (2003) Expression profile of genes from 12p in testicular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2-p12.1. Oncogene, 22 (12). pp. 1880-1891. ISSN 0950-9232

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Gain of 12p material is invariably associated with testicular germ cell tumors (TGCTs) of adolescents and adults, most usually as an isochromosome 12p. We analyzed TGCTs with i(12p) using a global approach to expression profiling targeting chromosomes (comparative expressed sequence hybridization, CESH). This indicated overexpression of genes from 12p11.2-p12.1 relative to testis tissue and fibroblasts. The nonseminoma subtype showed higher levels of expression than seminomas. Notably, 12p11.2-p12.1 is amplified in about 10% of TGCTs and CESH analysis of such amplicon cases showed high levels of overexpression from this region. Microarray analysis, including cDNA clones representing most UniGene clusters from 12p11.2-p12.1, was applied to DNA and RNA from 5 TGCTs with amplification of 12p11.2-p12.1 and seven TGCTs with gain of the entire short arm of chromosome 12. Expression profiles were consistent with the CESH data and overexpression of EST595078, MRPS35 and LDHB at 12p11.2-p12.1 was detected in most TGCTs. High-level overexpression of BCAT1 was specific to nonseminomas and overexpression of genes such as CMAS, EKI1, KRAS2, SURB7 and various ESTs correlated with their amplification. Genes such as CCND2, GLU3, LRP6 and HPH1 at 12p13 were also overexpressed. The overexpressed sequences identified, particularly those in the region amplified, represent candidate genes for involvement in TGCT development.

Item Type: Article
Additional Information: Funding Information: This work was supported by Cancer Research UK and the Dutch Cancer Society (Grant 98-1685).
Uncontrolled Keywords: amplification,candidate genes,comparative expressed sequence hybridization,isochromosome 12p,microarray expression profiling,testicular germ cell tumors of adolescents and adults,molecular biology,genetics,cancer research,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300/1312
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 18 Jul 2022 12:30
Last Modified: 23 Oct 2022 04:00
DOI: 10.1038/sj.onc.1206302

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