Overrepresentation of the short arm of chromosome 12 is related to invasive growth of human testicular seminomas and nonseminomas

Overrepresentation of 12p-sequences, mostly due to isochromosome formation, is the only consistent chromosomal alteration found in invasive testicular germ cell tumors of adolescents and young adults (TGCTs), both seminomas a nd the various histological elenlents of nonseminomas, The biological role of extra 12p in the pathogenesis of this cancer is unclear, and it is also unknown so far, whether it is an early event, i,e,, already present in carc inoma ill situ, or related to invasive growth. Using comparative genomic hy bridization (CGH) with DOP-PCR amplified DNA isolated from micro-dissected tumor cells, and double fluorescent in situ hybridization (FISH) on frozen tissue sections, we investigated the presence of overrepresentation of 12p sequences in different development stages of four seminomas and seven nonse minomas, in total 17 invasive components, in addition to the carcinoma in s itu of each. CGH demonstrated relative gain of 12p-sequences in all invasiv e components except one, confirmed by FISH in most samples. In contrast, no gain was found in the carcinoma in situ samples by any of the methods. The se findings show that overrepresentation of 12p is not an early event in th e development of TGCTs, but relates to invasive growth.