Epigenetic regulation during cancer transitions across 11 tumour types

被引：78

作者：

Terekhanova, Nadezhda V. ^{[1
,2
]}

Karpova, Alla ^{[1
,2
]}

Liang, Wen-Wei ^{[1
,2
]}

Strzalkowski, Alexander ^{[3
]}

Chen, Siqi ^{[1
,2
]}

Li, Yize ^{[1
,2
]}

Southard-Smith, Austin N. ^{[1
,2
]}

Iglesia, Michael D. ^{[1
,2
]}

Wendl, Michael C. ^{[1
,2
]}

Jayasinghe, Reyka G. ^{[1
,2
]}

Liu, Jingxian ^{[1
,2
]}

Song, Yizhe ^{[1
,2
]}

Cao, Song ^{[1
,2
]}

Houston, Andrew ^{[1
,2
]}

Liu, Xiuting ^{[1
]}

Wyczalkowski, Matthew A. ^{[1
,2
]}

Lu, Rita Jui-Hsien ^{[1
,2
]}

Caravan, Wagma ^{[1
,2
]}

Shinkle, Andrew ^{[1
]}

Al Deen, Nataly Naser ^{[1
,2
]}

Herndon, John M. ^{[4
,5
]}

Mudd, Jacqueline ^{[4
]}

Ma, Cong ^{[3
]}

Sarkar, Hirak ^{[3
]}

Sato, Kazuhito ^{[1
,2
]}

Ibrahim, Omar M. ^{[1
,2
]}

Mo, Chia-Kuei ^{[1
,2
]}

Chasnoff, Sara E. ^{[4
,5
]}

Porta-Pardo, Eduard ^{[6
,7
]}

Held, Jason M. ^{[1
,5
]}

Pachynski, Russell ^{[1
,5
]}

Schwarz, Julie K. ^{[8
]}

Gillanders, William E. ^{[4
,5
]}

Kim, Albert H. ^{[5
,9
]}

Vij, Ravi ^{[1
,5
]}

Dipersio, John F. ^{[1
,5
]}

Puram, Sidharth V. ^{[10
]}

Chheda, Milan G. ^{[1
,5
]}

Fuh, Katherine C. ^{[11
,12
]}

Denardo, David G. ^{[1
,5
]}

Fields, Ryan C. ^{[4
,5
]}

Chen, Feng ^{[1
,5
]}

Raphael, Benjamin J. ^{[3
]}

Ding, Li ^{[1
,2
,5
,13
]}

机构：

[1] Washington Univ, Dept Med, St Louis, MO 63130 USA

[2] Washington Univ, McDonnell Genome Inst, St Louis, MO 63130 USA

[3] Princeton Univ, Dept Comp Sci, Princeton, NJ 08544 USA

[4] Washington Univ, Dept Surg, St Louis, MO 63130 USA

[5] Washington Univ, Siteman Canc Ctr, St Louis, MO 63130 USA

[6] Josep Carreras Leukaemia Res Inst, Barcelona, Spain

[7] Barcelona Supercomp Ctr, Barcelona, Spain

[8] Washington Univ, Dept Radiat Oncol, St Louis, MO USA

[9] Washington Univ, Dept Neurol Surg, St Louis, MO USA

[10] Washington Univ, Dept Otolaryngol Head & Neck Surg, St Louis, MO USA

[11] Univ Calif San Francisco, Dept Obstet & Gynecol, San Francisco, CA USA

[12] Washington Univ, Dept Obstet & Gynecol, St Louis, MO USA

[13] Washington Univ, Dept Genet, St Louis, MO 63130 USA

来源：

NATURE | 2023年 / 623卷 / 7986期

关键词：

MULTIOMICS ANALYSIS REVEALS; TO-MESENCHYMAL TRANSITION; BREAST-CANCER; PROTEOGENOMIC CHARACTERIZATION; TRANSCRIPTION FACTORS; READ ALIGNMENT; CELL CARCINOMA; GROWTH; CHROMATIN; PROTEIN;

D O I：

10.1038/s41586-023-06682-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis1-4. 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. A pan-cancer epigenetic and transcriptomic atlas identifies epigenetic drivers associated with cancer transitions.

引用

页码：432 / +

页数：37

共 102 条

[1]

Aibar S, 2017, NAT METHODS, V14, P1083, DOI [10.1038/nmeth.4463, 10.1038/NMETH.4463]

[2] A gene-environment-induced epigenetic program initiates tumorigenesis [J].

Alonso-Curbelo, Direna ;

Ho, Yu-Jui ;

Burdziak, Cassandra ;

Maag, Jesper L. V. ;

Morris, John P. ;

Chandwani, Rohit ;

Chen, Hsuan-An ;

Tsanov, Kaloyan M. ;

Barriga, Francisco M. ;

Luan, Wei ;

Tasdemir, Nilgun ;

Livshits, Geulah ;

Azizi, Elham ;

Chun, Jaeyoung ;

Wilkinson, John E. ;

Mazutis, Linas ;

Leach, Steven D. ;

Koche, Richard ;

Pe'er, Dana ;

Lowe, Scott W. .

NATURE, 2021, 590 (7847) :642-648

[3]

Andreev J, 1999, MOL CELL BIOL, V19, P2338

[4]

Bailey MH, 2018, CELL, V173, P371, DOI [10.1016/j.cell.2018.02.060, 10.1016/j.cell.2018.07.034]

[5] Novel role of Engrailed 1 as a prosurvival transcription factor in basal-like breast cancer and engineering of interference peptides block its oncogenic function [J].

Beltran, A. S. ;

Graves, L. M. ;

Blancafort, P. .

ONCOGENE, 2014, 33 (39) :4767-4777

[6] Trimmomatic: a flexible trimmer for Illumina sequence data [J].

Bolger, Anthony M. ;

Lohse, Marc ;

Usadel, Bjoern .

BIOINFORMATICS, 2014, 30 (15) :2114-2120

[7]

Buenrostro JD, 2013, NAT METHODS, V10, P1213, DOI [10.1038/NMETH.2688, 10.1038/nmeth.2688]

[8] Epigenetic "Drivers" of Cancer [J].

Butera, Alessio ;

Melino, Gerry ;

Amelio, Ivano .

JOURNAL OF MOLECULAR BIOLOGY, 2021, 433 (15)

[9] Integrating single-cell transcriptomic data across different conditions, technologies, and species [J].

Butler, Andrew ;

Hoffman, Paul ;

Smibert, Peter ;

Papalexi, Efthymia ;

Satija, Rahul .

NATURE BIOTECHNOLOGY, 2018, 36 (05) :411-+

[10] Molecular Differences between Squamous Cell Carcinoma and Adenocarcinoma Cervical Cancer Subtypes: Potential Prognostic Biomarkers [J].

Campos-Parra, Alma D. ;

Perez-Quintanilla, Milagros ;

Daniel Martinez-Gutierrez, Antonio ;

Perez-Montiel, Delia ;

Coronel-Martinez, Jaime ;

Millan-Catalan, Oliver ;

Cantu De Leon, David ;

Perez-Plasencia, Carlos .

CURRENT ONCOLOGY, 2022, 29 (07) :4689-4702

← 1 2 3 4 5 6 7 8 9 10 →