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001-es BibID:	BIBFORM052712
Első szerző:	Kleinman, Claudia L.
Cím:	Fusion of TTYH1 with the C19MC microRNA cluster drives expression of a brain-specific DNMT3B isoform in the embryonal brain tumor ETMR / Claudia L. Kleinman, Noha Gerges, Simon Papillon-Cavanagh, Patrick Sin-Chan, Albena Pramatarova, Dong-Anh Khuong Quang, Véronique Adoue, Stephan Busche, Maxime Caron, Haig Djambazian, Amandine Bemmo, Adam M. Fontebasso, Tara Spence, Jeremy Schwartzentruber, Steffen Albrecht, Peter Hauser, Miklos Garami, Almos Klekner, Laszlo Bognar, Jose-Luis Montes, Alfredo Staffa, Alexandre Montpetit, Pierre Berube, Magdalena Zakrzewska, Krzysztof Zakrzewski, Pawel P. Liberski, Zhifeng Dong, Peter M. Siegel, Thomas Duchaine, Christian Perotti, Adam Fleming, Damien Faury, Marc Remke, Marco Gallo, Peter Dirks Michael D. Taylor, Robert Sladek, Tomi Pastinen, Jennifer A. Chan, Annie Huang, Jacek Majewski, Nada Jabado
Dátum:	2013
ISSN:	1061-4036
Megjegyzések:	Embryonal tumors with multilayered rosettes (ETMRs) are rare, deadly pediatric brain tumors characterized by high-level amplification of the microRNA cluster C19MC1, 2. We performed integrated genetic and epigenetic analyses of 12 ETMR samples and identified, in all cases, C19MC fusions to TTYH1 driving expression of the microRNAs. ETMR tumors, cell lines and xenografts showed a specific DNA methylation pattern distinct from those of other tumors and normal tissues. We detected extreme overexpression of a previously uncharacterized isoform of DNMT3B originating at an alternative promoter3 that is active only in the first weeks of neural tube development. Transcriptional and immunohistochemical analyses suggest that C19MC-dependent DNMT3B deregulation is mediated by RBL2, a known repressor of DNMT3B4, 5. Transfection with individual C19MC microRNAs resulted in DNMT3B upregulation and RBL2 downregulation in cultured cells. Our data suggest a potential oncogenic re-engagement of an early developmental program in ETMR via epigenetic alteration mediated by an embryonic, brain-specific DNMT3B isoform.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Nature Genetics. - 46 : 1 (2013), p. 39-44. -
További szerzők:	Gerges, Noha Papillon-Cavanagh, Simon Sin-Chan, Patrick Pramatarova, Albena Quang, Dong-Anh Khuong Adoue, Véronique Busche, Stephan Caron, Maxime Djambazian, Haig Bemmo, Amandine Fontebasso, Adam M. Spence, Tara Schwartzentruber, Jeremy Albrecht, Stephen Hauser Péter Garami Miklós Klekner Álmos (1970-) (idegsebész) Bognár László (1958-) (idegsebész, gyermekidegsebész) Montes, Jose-Luis Staffa, Alfredo Montpetit, Alexandre Berube, Pierre Zakrzewska, Magdalena Zakrzewski, Krzystof Liberski, Pawel P. Dong, Zhifeng Siegel, Peter Duchaine, Thomas Perotti, Christian Fleming, Adam Faury, Damien Remke, Marc Gallo, Marco Dirks, Peter Taylor, Michael D. Sladek, Robert Pastinen, Tomi Chan, Jennifer A. Huang, Annie Majewski, Jacek Jabado, Nada
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