Reviews of Chromosome Studies in Urological Tumors. III. Cytogenetics and Genes in Testicular Tumors

Abstract

Purpose: We reviewed available cytogenetic and m olecular findings in testicu lar germ cell tum ors, and th e ir possible application to clinical, pathological an d basic p aram eters.M aterials and Methods: Findings in th e lite ra tu re on te stic u la r germ cell tum ors as w ell as those from our laboratory were sum m arized, including a listin g of th e cytogenetic findings on testicu lar germ cell tum ors to date w ith some illu stratio n s,Results: Testicular germ cell tum ors are characterized in m ost cases by the presence of an i(12p) isochromosome. In tum ors w ithout such an abnorm al chrom osom e studies u sin g fluores cence in situ hybridization and m olecular approaches have d em o n strated eith er m asking of th e i(12p) or th e presence of extra 12p sequences in the karyotype. A lthough testicu lar germ cell tum ors are often associated w ith chromosome changes in addition to th e i(12p), no o th er specifically recu rren t stru ctu ral chromosome changes have b e e n found. B ased on th e cytogenetic and m olecular findings in testicular germ cell tum ors, a hy p o th etical schem e for th e genetic events leading to these tum ors is presented.Conclusions: The genetic events leading to genesis of te stic u la r germ cell tum ors in m en a p p ea r to be related to aneuploidization followed by th e form ation of a n i(12p) isochrom osome, th e la tte r characterizing the preponderant num ber of te stic u la r germ cell tum ors. The exact role of th e i(12p) isochromosome in testicular germ cell tum or p ath o g en esis rem ain s to be determ ined, as is tru e of the genes involved in or affected by these tum ors. B ased on p re se n tly available in fo rm a tion, a hypothetical pathogenetic and oncogenetic model for th e developm ent of te stic u la r germ cell tum ors is presented.

The CDK inhibitor p27 enhances neural differentiation in pluripotent NTERA2 human EC cells, but does not permit differentiation of 2102Ep nullipotent human EC cells

“…Human GCT are characterised by the frequent amplification of the short arm of chromosome 12 (12p), usually in the form of one or more isochromosomes (12p) (Atkin and Baker, 1982;Mostert et al, 1996;Sandberg et al, 1996), and of the long arm of chromosome 17 (17q) (Kraggerud et al, 2002). A number of candidate genes that might play a role in this selection have been identified on chromosomes 17q and 12p.…”

Large cell carcinoma of the lung mimicking a germ cell tumor: The potential value of chromosome analysis

“…Hematologic neoplasias containing i(12)p have been associated with concurrent germ-cell tumors [21]. Germ cell tumor carcinogenesis is thought to result from aneuploidy followed by generation of an i(12)p or other chromosome 12 abnormalities [22]. The genes affected by this process still remain unknown.…”

“…With the limited number of copies, the presence of i(12)p was interpreted cautiously, since the appearance of an i(12)p chromosome can occasionally result from the juxtaposition of chromosome 12 signals in a nucleus. The presence of multiple copies of chromosome 12p is a sensitive yet not specific marker of GCT [15,22].…”

Molecular Genetic Parameters in Pathogenesis and Prognosis of Testicular Germ Cell Tumors

“…3p, 9p, 9q, 10q, 11p, 11q and 17p encoding already known and putative tumor suppressor genes such as RB, DCC, NME, p53 and p16 have been found; furthermore, several novel sites have been identified by detailed allelotype analysis using loss–of–heterozygosity (LOH) assays: 2p, 3q, 5p, 12q, 18p and 20p [8, 9, 10, 11, 12, 13]. …”