Naslov
Epimutations in teratocarcinoma development

Autori
Sinčić, Nino ; Vlahović, Maja ; Bulić-Jakuš, Floriana ; Herceg, Zdenko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of abstracts of European Human Genetics conference / - , 2011, 383-383

Skup
European Human Genetics Conference 2011

Mjesto i datum
Amsterdam, Nizozemska, 28.05.2011. - 31.05.2011

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
teratocarcinoma; methylation; Oct 3/4; Nanog

Sažetak
Testicular germ cell tumors (TGCT) are the most frequent cancers in young men. Present study takes advantage of the experimental mouse teratocarcinoma (TCa) model, a powerful tool for detecting /monitoring alterations, including epigenetic disruptions, during a timeframe of cancer development in vivo. TCas were obtained by transplanting 7, 5–days-old C3H embryos under the kidney capsule of syngeneic adults. Animals were killed after 2, 4, 6 or 8 weeks. Bisulfite modification of gDNA was performed and DNA methylation status was analyzed by pyrosequencing assay. TCas exhibited two time points of intensive growth ; in the 4th and 8th week. Significant changes in Oct3/4 DNA methylation were found during 8 weeks TCa development. From the 4th week, TCas showed significant Oct3/4 hypermethylation when compared to testicular tissue. Only 8 weeks old TCas showed strong negative correlation between Oct3/4 DNA methylation and TCa growth. Significant changes in DNA methylation of Nanog promoter were found during 8 weeks TCa development. All TCas showed significant Nanog hypomethylation when compared to testicular tissue. We noticed negative correlation between TCa weight and Nanog DNA methylation in 4 weeks old TCas. Scgb3a1 and Prss21 showed constant hypermethylation in TCas when compared to normal testicular tissue. We suggest that Nanog DNA hypomethylation represents an early cancerogenic force pushing cells into TGCT/teratocarcinoma development while Oct3/4 DNA hypermethylation seems to compensate cancer initiation and inhibit cancer progression. If Oct3/4 is not methylated, intense cancer progression can take place. Genes involved in testicular differentiation seems to remain suppressed during TCa cancerogenesis.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA