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Integrated analyses highlight interactions between the three-dimensional genome and DNA, RNA and epigenomic alterations in metastatic prostate cancer.
Zhao, Shuang G; Bootsma, Matthew; Zhou, Stanley; Shrestha, Raunak; Moreno-Rodriguez, Thaidy; Lundberg, Arian; Pan, Chu; Arlidge, Christopher; Hawley, James R; Foye, Adam; Weinstein, Alana S; Sjöström, Martin; Zhang, Meng; Li, Haolong; Chesner, Lisa N; Rydzewski, Nicholas R; Helzer, Kyle T; Shi, Yue; Lynch, Molly; Dehm, Scott M; Lang, Joshua M; Alumkal, Joshi J; He, Hansen H; Wyatt, Alexander W; Aggarwal, Rahul; Zwart, Wilbert; Small, Eric J; Quigley, David A; Lupien, Mathieu; Feng, Felix Y.
Afiliación
  • Zhao SG; Department of Human Oncology, University of Wisconsin-Madison, Madison, WI, USA.
  • Bootsma M; Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Zhou S; William S. Middleton Memorial Veterans Hospital, Madison, Madison, WI, USA.
  • Shrestha R; Department of Human Oncology, University of Wisconsin-Madison, Madison, WI, USA.
  • Moreno-Rodriguez T; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • Lundberg A; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • Pan C; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Arlidge C; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Hawley JR; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Foye A; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Weinstein AS; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Sjöström M; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Zhang M; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • Li H; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • Chesner LN; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • Rydzewski NR; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • Helzer KT; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • Shi Y; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • Lynch M; Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Dehm SM; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Lang JM; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Alumkal JJ; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • He HH; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Wyatt AW; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Aggarwal R; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Zwart W; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Small EJ; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Quigley DA; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Lupien M; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Feng FY; Department of Human Oncology, University of Wisconsin-Madison, Madison, WI, USA.
Nat Genet ; 56(8): 1689-1700, 2024 Aug.
Article en En | MEDLINE | ID: mdl-39020220
ABSTRACT
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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Metilación de ADN / 5-Metilcitosina Límite: Humans / Male Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Metilación de ADN / 5-Metilcitosina Límite: Humans / Male Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos