TY - JOUR
T1 - Epigenetic regulation during cancer transitions across 11 tumour types
AU - Terekhanova, Nadezhda V.
AU - Karpova, Alla
AU - Liang, Wen Wei
AU - Strzalkowski, Alexander
AU - Chen, Siqi
AU - Li, Yize
AU - Southard-Smith, Austin N.
AU - Iglesia, Michael D.
AU - Wendl, Michael C.
AU - Jayasinghe, Reyka G.
AU - Liu, Jingxian
AU - Song, Yizhe
AU - Cao, Song
AU - Houston, Andrew
AU - Liu, Xiuting
AU - Wyczalkowski, Matthew A.
AU - Lu, Rita Jui Hsien
AU - Caravan, Wagma
AU - Shinkle, Andrew
AU - Naser Al Deen, Nataly
AU - Herndon, John M.
AU - Mudd, Jacqueline
AU - Ma, Cong
AU - Sarkar, Hirak
AU - Sato, Kazuhito
AU - Ibrahim, Omar M.
AU - Mo, Chia Kuei
AU - Chasnoff, Sara E.
AU - Porta-Pardo, Eduard
AU - Held, Jason M.
AU - Pachynski, Russell
AU - Schwarz, Julie K.
AU - Gillanders, William E.
AU - Kim, Albert H.
AU - Vij, Ravi
AU - DiPersio, John F.
AU - Puram, Sidharth V.
AU - Chheda, Milan G.
AU - Fuh, Katherine C.
AU - DeNardo, David G.
AU - Fields, Ryan C.
AU - Chen, Feng
AU - Raphael, Benjamin J.
AU - Ding, Li
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/11/9
Y1 - 2023/11/9
N2 - 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 1–4. 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.
AB - 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 1–4. 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.
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U2 - 10.1038/s41586-023-06682-5
DO - 10.1038/s41586-023-06682-5
M3 - Article
C2 - 37914932
AN - SCOPUS:85175380275
SN - 0028-0836
VL - 623
SP - 432
EP - 441
JO - Nature
JF - Nature
IS - 7986
ER -