Publications

Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer

Abstract

DNA replication timing is known to facilitate the establishment of the epigenome, however, the intimate connection between replication timing and changes to the genome and epigenome in cancer remain largely uncharacterised. Here, we perform Repli-Seq and integrated epigenome analyses and demonstrate that genomic regions that undergo long-range epigenetic deregulation in prostate cancer also show concordant differences in replication timing. A subset of altered replication timing domains are conserved across cancers from different tissue origins. Notably, late-replicating regions in cancer cells display a loss of DNA methylation, and a switch in heterochromatin features from H3K9me3-marked constitutive to H3K27me3-marked facultative heterochromatin. Finally, analysis of 214 prostate and 35 breast cancer genomes reveal that late-replicating regions are prone to cis and early-replication to trans chromosomal rearrangements. Together, our data suggests that the nature of chromosomal rearrangement in cancer is related to the spatial and temporal positioning and altered epigenetic states of early-replicating compared to late-replicating loci.

Type Journal
ISBN 2041-1723 (Electronic) 2041-1723 (Linking)
Authors Du, Q.; Bert, S. A.; Armstrong, N. J.; Caldon, C. E.; Song, J. Z.; Nair, S. S.; Gould, C. M.; Luu, P. L.; Peters, T.; Khoury, A.; Qu, W.; Zotenko, E.; Stirzaker, C.; Clark, S. J.
Responsible Garvan Author Prof Susan Clark
Publisher Name Nature Communications
Published Date 2019-01-24
Published Volume 10
Published Issue 1
Published Pages 416
Status Published in-print
DOI 10.1038/s41467-019-08302-1
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/30679435