Integrated analyses highlight interactions between the three-dimensional genome and DNA, RNA and epigenomic alterations in metastatic prostate cancer-Reference-Cited by-同舟云学术

Integrated analyses highlight interactions between the three-dimensional genome and DNA, RNA and epigenomic alterations in metastatic prostate cancer

Published:2024-07-17 Issue:8 Volume:56 Page:1689-1700
ISSN:1061-4036
Container-title:Nature Genetics
language:en
Short-container-title:Nat Genet

Author:

Zhao Shuang G.^ORCID,Bootsma Matthew,Zhou Stanley^ORCID,Shrestha Raunak^ORCID,Moreno-Rodriguez Thaidy^ORCID,Lundberg Arian^ORCID,Pan Chu,Arlidge Christopher,Hawley James R.,Foye Adam,Weinstein Alana S.^ORCID,Sjöström Martin^ORCID,Zhang Meng^ORCID,Li Haolong^ORCID,Chesner Lisa N.,Rydzewski Nicholas R.,Helzer Kyle T.^ORCID,Shi Yue^ORCID, ,Bailey Adina M.,Zhang Li,Beer Tomasz M.,Thomas George,Chi Kim N.,Gleave Martin,Zoubeidi Amina,Reiter Robert E.,Rettig Matthew B.,Witte Owen,Bose Rohit,Huang Franklin W.,Fong Larry,Lara Primo N.,Evans Christopher P.,Huang Jiaoti,Lynch Molly,Dehm Scott M.^ORCID,Lang Joshua M.^ORCID,Alumkal Joshi J.^ORCID,He Hansen H.^ORCID,Wyatt Alexander W.^ORCID,Aggarwal Rahul^ORCID,Zwart Wilbert^ORCID,Small Eric J.^ORCID,Quigley David A.^ORCID,Lupien Mathieu,Feng Felix Y.^ORCID

Abstract

AbstractThe impact of variations in the three-dimensional structure of the genome has been recognized, but solid cancer tissue studies are limited. Here, we performed integrated deep Hi-C sequencing with matched whole-genome sequencing, whole-genome bisulfite sequencing, 5-hydroxymethylcytosine (5hmC) sequencing and RNA sequencing across a cohort of 80 biopsy samples from patients with metastatic castration-resistant prostate cancer. Dramatic differences were present in gene expression, 5-methylcytosine/5hmC methylation and in structural variation versus mutation rate between A and B (open and closed) chromatin compartments. A subset of tumors exhibited depleted regional chromatin contacts at the AR locus, linked to extrachromosomal circular DNA (ecDNA) and worse response to AR signaling inhibitors. We also identified topological subtypes associated with stark differences in methylation structure, gene expression and prognosis. Our data suggested that DNA interactions may predispose to structural variant formation, exemplified by the recurrent TMPRSS2–ERG fusion. This comprehensive integrated sequencing effort represents a unique clinical tumor resource.

Publisher

Springer Science and Business Media LLC

Link

https://www.nature.com/articles/s41588-024-01826-3.pdf

Reference85 articles.

1. Abeshouse, A. et al. The molecular taxonomy of primary prostate cancer. Cell 163, 1011–1025 (2015).

2. Pomerantz, M. M. et al. The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis. Nat. Genet. 47, 1346–1351 (2015).

3. Armenia, J. et al. The long tail of oncogenic drivers in prostate cancer. Nat. Genet. 50, 645–651 (2018).

4. Quigley, D. A. et al. Genomic hallmarks and structural variation in metastatic prostate cancer. Cell 174, 758–769 (2018).

5. Zhao, S. G. et al. The DNA methylation landscape of advanced prostate cancer. Nat. Genet. 52, 778–789 (2020).