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001-es BibID:	BIBFORM074473
035-os BibID:	(WoS)000444174100032 (Scopus)85050544773
Első szerző:	Patten, Darren K.
Cím:	Enhancer mapping uncovers phenotypic heterogeneity and evolution in patients with luminal breast cancer / Darren K. Patten, Giacomo Corleone, Balázs Győrffy, Ylenia Perone, Neil Slaven, Iros Barozzi, Edina Erdős, Alina Saiakhova, Kate Goddard, Andrea Vingiani, Sami Shousha, Lőrinc Sándor Pongor, Dimitri J. Hadjiminas, Gaia Schiavon, Peter Barry, Carlo Palmieri, Raul C. Coombes, Peter Scacheri, Giancarlo Pruneri, Luca Magnani
Dátum:	2018
ISSN:	1078-8956
Megjegyzések:	The degree of intrinsic and interpatient phenotypic heterogeneity and its role in tumor evolution is poorly understood. Phenotypic drifts can be transmitted via inheritable transcriptional programs. Cell-type specific transcription is maintained through the activation of epigenetically defined regulatory regions including promoters and enhancers. Here we have annotated the epigenome of 47 primary and metastatic estrogen-receptor (ERα)-positive breast cancer clinical specimens and inferred phenotypic heterogeneity from the regulatory landscape, identifying key regulatory elements commonly shared across patients. Shared regions contain a unique set of regulatory information including the motif for transcription factor YY1. We identify YY1 as a critical determinant of ERα transcriptional activity promoting tumor growth in most luminal patients. YY1 also contributes to the expression of genes mediating resistance to endocrine treatment. Finally, we used H3K27ac levels at active enhancer elements as a surrogate of intra-tumor phenotypic heterogeneity to track the expansion and contraction of phenotypic subpopulations throughout breast cancer progression. By tracking the clonality of SLC9A3R1-positive cells, a bona fide YY1-ERα-regulated gene, we show that endocrine therapies select for phenotypic clones under-represented at diagnosis. Collectively, our data show that epigenetic mechanisms significantly contribute to phenotypic heterogeneity and evolution in systemically treated breast cancer patients.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk epigenetic breast cancer tumor evolution
Megjelenés:	Nature Medicine. - 24 : 9 (2018), p. 1469-1480. -
További szerzők:	Corleone, Giacomo Győrffy Balázs Perone, Ylenia Slaven, Neil Barozzi, Iros Erdős Edina (1989-) (klinikai laboratóriumi kutató) Saiakhova, Alina Goddard, Kate Vingiani, Andrea Shousha, Sami Pongor Lőrinc Sándor Hadjiminas, Dimitri J. Schiavon, Gaia Barry, Peter Palmieri, Carlo Coombes, Raul C. Scacheri, Peter Pruneri, Giancarlo Magnani, Luca
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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