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

Autor:	Zhao SG; Department of Human Oncology, University of Wisconsin-Madison, Madison, WI, USA.; Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.; William S. Middleton Memorial Veterans Hospital, Madison, Madison, WI, USA., Bootsma M; Department of Human Oncology, University of Wisconsin-Madison, Madison, WI, USA., Zhou S; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada., Shrestha R; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA., Moreno-Rodriguez T; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA., Lundberg A; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA., Pan C; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada., Arlidge C; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada., Hawley JR; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada., Foye A; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.; Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA., Weinstein AS; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA., Sjöström M; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA., Zhang M; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA., Li H; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA., Chesner LN; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA., Rydzewski NR; Department of Human Oncology, University of Wisconsin-Madison, Madison, WI, USA.; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Helzer KT; Department of Human Oncology, University of Wisconsin-Madison, Madison, WI, USA., Shi Y; Department of Human Oncology, University of Wisconsin-Madison, Madison, WI, USA., Lynch M; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA., Dehm SM; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.; Department of Urology, University of Minnesota, Minneapolis, MN, USA., Lang JM; Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.; Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA., Alumkal JJ; Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA., He HH; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada., Wyatt AW; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.; Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada., Aggarwal R; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.; Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA., Zwart W; Netherlands Cancer Institute, Oncode Institute, Amsterdam, the Netherlands., Small EJ; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.; Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA., Quigley DA; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.; Department of Urology, University of California San Francisco, San Francisco, CA, USA., Lupien M; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada., Feng FY; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA. Felix.Feng@ucsf.edu.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. Felix.Feng@ucsf.edu.; Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA. Felix.Feng@ucsf.edu.; Department of Urology, University of California San Francisco, San Francisco, CA, USA. Felix.Feng@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Nature genetics [Nat Genet] 2024 Aug; Vol. 56 (8), pp. 1689-1700. Date of Electronic Publication: 2024 Jul 17.
DOI:	10.1038/s41588-024-01826-3
Abstrakt:	The 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. (© 2024. The Author(s).)
Databáze:	MEDLINE
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