DNA methylation changes in human testicular cancer.
We previously reported an X/Y imbalance with a relative excess of X- and a relative deficiency of Y-chromosomal DNA in three out of nine testicular tumors of germ cell origin. To study the implications of those changes the methylation status of DNA from seven of the tumors was explored by HpaII/MspI analysis. The 5' regions of the hypoxanthine phosphoribosyltransferase (HPRT) and the phosphoglycerate kinase (PGK) gene loci exhibited main patterns suggestive of active X chromosomes in the tumors. However, a minority of the HPRT loci of one teratocarcinoma with an increased dosage of the X chromosome, as well as one additional teratocarcinoma, revealed patterns analogous to inactive X chromosomes in females. Using probes from several chromosomes it was subsequently found that the teratocarcinoma tumors (3/3) were characterized by generalized hypermethylation. On the contrary, the seminomas showed variable hypomethylation (4/5) or virtually complete demethylation (1/5). The seminoma with the most extensive hypomethylation was disseminated (stage III), whereas the other seminomas were local (stage I). These findings suggest that DNA methylation may play a role in the developmental pathways leading to different histologic types of testicular tumors of germ cell origin. The HPRT results imply that the consequences of extra X chromosomes--a frequent finding in testicular tumors--may be modulated by mechanisms, such as DNA methylation, that control gene activity.
Peltomäki
P
P
Department of Medical Genetics, University of Helsinki, Finland.
D004247:DNA / Q000378:metabolism*; D015342:DNA Probes; D004407:Dysgerminoma / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008297:Male; D008745:Methylation; D015183:Restriction Mapping; D013724:Teratoma / Q000235:genetics / Q000378:metabolism*; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism*; D014960:X Chromosome; D014998:Y Chromosome
D015342:DNA Probes; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase