Imperial College London
Alternate

ProfessorLucaMagnani

Faculty of Medicine, Department of Surgery & Cancer

Honorary Principal Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 2808l.magnani CV

 
 
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Location

 

137ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Heide:2022:10.1038/s41586-022-05202-1,
author = {Heide, T and Househam, J and Cresswell, GD and Spiteri, I and Lynn, C and Mossner, M and Kimberley, C and Fernandez-Mateos, J and Chen, B and Zapata, L and James, C and Barozzi, I and Chkhaidze, K and Nichol, D and Gunasri, V and Berner, A and Schmidt, M and Lakatos, E and Baker, A-M and Costa, H and Mitchinson, M and Piazza, R and Jansen, M and Caravagna, G and Ramazzotti, D and Shibata, D and Bridgewater, J and Rodriguez-Justo, M and Magnani, L and Graham, TA and Sottoriva, A},
doi = {10.1038/s41586-022-05202-1},
journal = {Nature},
pages = {733--743},
title = {The co-evolution of the genome and epigenome in colorectal cancer},
url = {http://dx.doi.org/10.1038/s41586-022-05202-1},
volume = {611},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Colorectal malignancies are a leading cause of cancer-related death1 and have undergone extensive genomic study2,3. However, DNA mutations alone do not fully explain malignant transformation4,5,6,7. Here we investigate the co-evolution of the genome and epigenome of colorectal tumours at single-clone resolution using spatial multi-omic profiling of individual glands. We collected 1,370 samples from 30 primary cancers and 8 concomitant adenomas and generated 1,207 chromatin accessibility profiles, 527 whole genomes and 297 whole transcriptomes. We found positive selection for DNA mutations in chromatin modifier genes and recurrent somatic chromatin accessibility alterations, including in regulatory regions of cancer driver genes that were otherwise devoid of genetic mutations. Genome-wide alterations in accessibility for transcription factor binding involved CTCF, downregulation of interferon and increased accessibility for SOX and HOX transcription factor families, suggesting the involvement of developmental genes during tumourigenesis. Somatic chromatin accessibility alterations were heritable and distinguished adenomas from cancers. Mutational signature analysis showed that the epigenome in turn influences the accumulation of DNA mutations. This study provides a map of genetic and epigenetic tumour heterogeneity, with fundamental implications for understanding colorectal cancer biology.
AU  - Heide,T
AU  - Househam,J
AU  - Cresswell,GD
AU  - Spiteri,I
AU  - Lynn,C
AU  - Mossner,M
AU  - Kimberley,C
AU  - Fernandez-Mateos,J
AU  - Chen,B
AU  - Zapata,L
AU  - James,C
AU  - Barozzi,I
AU  - Chkhaidze,K
AU  - Nichol,D
AU  - Gunasri,V
AU  - Berner,A
AU  - Schmidt,M
AU  - Lakatos,E
AU  - Baker,A-M
AU  - Costa,H
AU  - Mitchinson,M
AU  - Piazza,R
AU  - Jansen,M
AU  - Caravagna,G
AU  - Ramazzotti,D
AU  - Shibata,D
AU  - Bridgewater,J
AU  - Rodriguez-Justo,M
AU  - Magnani,L
AU  - Graham,TA
AU  - Sottoriva,A
DO  - 10.1038/s41586-022-05202-1
EP  - 743
PY  - 2022///
SN  - 0028-0836
SP  - 733
TI  - The co-evolution of the genome and epigenome in colorectal cancer
T2  - Nature
UR  - http://dx.doi.org/10.1038/s41586-022-05202-1
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000873432900005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://www.nature.com/articles/s41586-022-05202-1
UR  - http://hdl.handle.net/10044/1/101788
VL  - 611
ER  -
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