Identification of genes differentially expressed in testes containing carcinoma in situ.

Virtually all testicular germ cell tumours originate from a common precursor, the carcinoma in situ (CIS) cell. The precise nature of the molecular mechanisms leading to CIS remains largely unknown. We performed the first systematic analysis of gene expression in testis with CIS compared to normal testis by the differential display (DDRT-PCR) method, with subsequent analysis by RT-PCR and in situ hybridization (ISH). In tissue containing CIS we identified overexpression of 28 mRNA, some previously reported in CIS and a number of genes not previously described in germ cell neoplasia, including the novel expressed sequence tag (EST) OIC1 (Overexpressed In CIS). The genes could be grouped functionally into genes involved in cell growth, proliferation, differentiation, immunological response, and genes with unknown biological function. Examples of overexpressed genes are SFRP1 that is involved in Wnt signalling and IGFBP6, which is of importance for fetal growth and inhibits cell growth through insulin-like growth factor-II. ISH analysis showed that both mRNA were localized to CIS cells. The results of our search for differentially expressed genes in CIS demonstrated a number of genes linked to testicular development (e.g. DCN, IGFBP6, SFRP1, SALL1), supporting our hypothesis that the origin of CIS is probably associated with disturbances of the fetal development of the testis.