Epigenetic regulation during cancer transitions across 11 tumour types
Terekhanova, Nadezhda V. (Washington University in St Louis)
Karpova, Alla (Washington University in St Louis)
Liang, Wen Wei (Washington University in St Louis)
Strzalkowski, Alexander (Department of Computer Science. Princeton University)
Chen, Siqi (Washington University in St Louis)
Li, Yize (Washington University in St Louis)
Southard-Smith, Austin N. (Washington University in St Louis)
Iglesia, Michael D. (Washington University in St Louis)
Wendl, Michael C. (Washington University in St Louis)
Jayasinghe, Reyka G. (Washington University in St Louis)
Liu, Jingxian (Washington University in St Louis)
Song, Yizhe (Washington University in St Louis)
Cao, Song (Washington University in St Louis)
Houston, Andrew (Washington University in St Louis)
Liu, Xiuting (Department of Medicine. Washington University in St Louis)
Wyczalkowski, Michael A. (Washington University in St Louis)
Lu, Rita Jui-Hsien (Washington University in St Louis)
Caravan, Wagma (Washington University in St Louis)
Shinkle, Andrew (Department of Medicine. Washington University in St Louis)
Naser Al Deen, Nataly (Washington University in St Louis)
Herndon, John M. (Washington University in St Louis)
Mudd, Jacqueline (Department of Surgery. Washington University in St Louis)
Ma, Cong (Department of Computer Science. Princeton University)
Sarkar, Hirak (Department of Computer Science. Princeton University)
Sato, Kazuhito (Washington University in St Louis)
Ibrahim, Omar.M. (Washington University in St Louis)
Mo, Chia-Kuei (Washington University in St Louis)
Chasnoff, Sara E. (Washington University in St Louis)
Porta-Pardo, Eduard (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Held, Jasson M. (Washington University in St Louis)
Pachynski, Russell (Washington University in St Louis)
Schwarz, Julie K. (Department of Radiation Oncology. Washington University in St Louis)
Gillanders, William E. (Washington University in St Louis)
Kim, Albert H. (Department of Neurological Surgery. Washington University in St Louis)
Vij, Ravi (Washington University in St Louis)
DiPersio, John.F. (Washington University in St Louis)
Puram, Sidharth V. (Department of Otolaryngology-Head & Neck Surgery. Washington University in St Louis)
Chheda, Milan G. (Washington University in St Louis)
Fuh, Katherine C. (Department of Obstetrics and Gynecology. Washington University in St Louis)
DeNardo, David G. (Washington University in St Louis)
Fields, Ryan C. (Washington University in St Louis)
Chen, Feng (Washington University in St Louis)
Raphael, Benjamin J. (Department of Computer Science. Princeton University)
Ding, Li (Department of Genetics. Washington University in St Louis)

Data:	2023
Resum:	Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis. Although the genetic contributions to oncogenic transitions have been investigated, epigenetic drivers remain less understood. Here we constructed a pan-cancer epigenetic and transcriptomic atlas using single-nucleus chromatin accessibility data (using single-nucleus assay for transposase-accessible chromatin) from 225 samples and matched single-cell or single-nucleus RNA-sequencing expression data from 206 samples. With over 1 million cells from each platform analysed through the enrichment of accessible chromatin regions, transcription factor motifs and regulons, we identified epigenetic drivers associated with cancer transitions. Some epigenetic drivers appeared in multiple cancers (for example, regulatory regions of ABCC1 and VEGFA; GATA6 and FOX-family motifs), whereas others were cancer specific (for example, regulatory regions of FGF19, ASAP2 and EN1, and the PBX3 motif). Among epigenetically altered pathways, TP53, hypoxia and TNF signalling were linked to cancer initiation, whereas oestrogen response, epithelial-mesenchymal transition and apical junction were tied to metastatic transition. Furthermore, we revealed a marked correlation between enhancer accessibility and gene expression and uncovered cooperation between epigenetic and genetic drivers. This atlas provides a foundation for further investigation of epigenetic dynamics in cancer transitions.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Nature, Vol. 623 Núm. 7986 (september 2023) , p. 432-441, ISSN 1476-4687

DOI: 10.1038/s41586-023-06682-5
PMID: 37914932

37 p, 20.5 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Institut de Recerca contra la Leucèmia Josep Carreras
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