Universität zu Köln

Haensel-Hertsch, Robert ORCID: 0000-0002-2835-4471, Simeone, Angela, Shea, Abigail, Hui, Winnie W. I., Zyner, Katherine G., Marsico, Giovanni, Rueda, Oscar M., Bruna, Alejandra, Martin, Alistair, Zhang, Xiaoyun ORCID: 0000-0002-4132-3573, Adhikari, Santosh ORCID: 0000-0002-1501-2106, Tannahill, David, Caldas, Carlos ORCID: 0000-0003-3547-1489 and Balasubramanian, Shankar (2020). Landscape of G-quadruplex DNA structural regions in breast cancer. Nature Genet., 52 (9). S. 878 - 892. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-1718

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Abstract

Response and resistance to anticancer therapies vary due to intertumor and intratumor heterogeneity(1). Here, we map differentially enriched G-quadruplex (G4) DNA structure-forming regions ( increment G4Rs) in 22 breast cancer patient-derived tumor xenograft (PDTX) models. increment G4Rs are associated with the promoters of highly amplified genes showing high expression, and with somatic single-nucleotide variants. Differences in Delta G4R landscapes reveal seven transcription factor programs across PDTXs. increment G4R abundance and locations stratify PDTXs into at least three G4-based subtypes. increment G4Rs in most PDTXs (14 of 22) were found to associate with more than one breast cancer subtype, which we also call an integrative cluster (IC)(2). This suggests the frequent coexistence of multiple breast cancer states within a PDTX model, the majority of which display aggressive triple-negative IC10 gene activity. Short-term cultures of PDTX models with increased increment G4R levels are more sensitive to small molecules targeting G4 DNA. Thus, G4 landscapes reveal additional IC-related intratumor heterogeneity in PDTX biopsies, improving breast cancer stratification and potentially identifying new treatment strategies. Quantitative ChIP-seq analysis maps G-quadruplex (G4) DNA structures in breast cancer patient-derived tumor xenograft (PDTX) models. G4-based subtypes highlight additional tumor heterogeneity in the integrative cluster (IC) system.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Haensel-Hertsch, Robert UNSPECIFIED orcid.org/0000-0002-2835-4471 UNSPECIFIED Simeone, Angela UNSPECIFIED UNSPECIFIED UNSPECIFIED Shea, Abigail UNSPECIFIED UNSPECIFIED UNSPECIFIED Hui, Winnie W. I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zyner, Katherine G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Marsico, Giovanni UNSPECIFIED UNSPECIFIED UNSPECIFIED Rueda, Oscar M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruna, Alejandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin, Alistair UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhang, Xiaoyun UNSPECIFIED orcid.org/0000-0002-4132-3573 UNSPECIFIED Adhikari, Santosh UNSPECIFIED orcid.org/0000-0002-1501-2106 UNSPECIFIED Tannahill, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Caldas, Carlos UNSPECIFIED orcid.org/0000-0003-3547-1489 UNSPECIFIED Balasubramanian, Shankar UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-324059
DOI:	10.1038/s41588-020-0672-8
Journal or Publication Title:	Nature Genet.
Volume:	52
Number:	9
Page Range:	S. 878 - 892
Date:	2020
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1546-1718
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TRIGGERS Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32405