Your browser doesn't support javascript.
loading
Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer.
Quigley, David A; Dang, Ha X; Zhao, Shuang G; Lloyd, Paul; Aggarwal, Rahul; Alumkal, Joshi J; Foye, Adam; Kothari, Vishal; Perry, Marc D; Bailey, Adina M; Playdle, Denise; Barnard, Travis J; Zhang, Li; Zhang, Jin; Youngren, Jack F; Cieslik, Marcin P; Parolia, Abhijit; Beer, Tomasz M; Thomas, George; Chi, Kim N; Gleave, Martin; Lack, Nathan A; Zoubeidi, Amina; Reiter, Robert E; Rettig, Matthew B; Witte, Owen; Ryan, Charles J; Fong, Lawrence; Kim, Won; Friedlander, Terence; Chou, Jonathan; Li, Haolong; Das, Rajdeep; Li, Hui; Moussavi-Baygi, Ruhollah; Goodarzi, Hani; Gilbert, Luke A; Lara, Primo N; Evans, Christopher P; Goldstein, Theodore C; Stuart, Joshua M; Tomlins, Scott A; Spratt, Daniel E; Cheetham, R Keira; Cheng, Donavan T; Farh, Kyle; Gehring, Julian S; Hakenberg, Jörg; Liao, Arnold; Febbo, Philip G.
Afiliación
  • Quigley DA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA; Department of Epidemiology and Biostatistics, UCSF, San Francisco, CA, USA.
  • Dang HX; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO, USA; Department of Internal Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Zhao SG; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
  • Lloyd P; Division of Hematology and Oncology, Department of Medicine, UCSF, San Francisco, CA, USA.
  • Aggarwal R; Division of Hematology and Oncology, Department of Medicine, UCSF, San Francisco, CA, USA.
  • Alumkal JJ; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA.
  • Foye A; Division of Hematology and Oncology, Department of Medicine, UCSF, San Francisco, CA, USA.
  • Kothari V; Department of Radiation Oncology, UCSF, San Francisco, CA, USA.
  • Perry MD; Department of Radiation Oncology, UCSF, San Francisco, CA, USA.
  • Bailey AM; Division of Hematology and Oncology, Department of Medicine, UCSF, San Francisco, CA, USA.
  • Playdle D; Division of Hematology and Oncology, Department of Medicine, UCSF, San Francisco, CA, USA.
  • Barnard TJ; Department of Radiation Oncology, UCSF, San Francisco, CA, USA.
  • Zhang L; Division of Hematology and Oncology, Department of Medicine, UCSF, San Francisco, CA, USA.
  • Zhang J; Cancer Biology Division, Department of Radiation Oncology, Washington University in St. Louis, MO USA; Institute for Informatics (I(2)), Washington University in St. Louis, MO.
  • Youngren JF; Division of Hematology and Oncology, Department of Medicine, UCSF, San Francisco, CA, USA.
  • Cieslik MP; Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Ann Arbor, MI, USA.
  • Parolia A; Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Ann Arbor, MI, USA.
  • Beer TM; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Thomas G; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Department of Pathology, Oregon Health and Science University, Portland, OR, USA.
  • Chi KN; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada; British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC, Canada.
  • Gleave M; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Lack NA; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Zoubeidi A; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Reiter RE; Jonsson Comprehensive Cancer Center, Department of Urology, UCLA, Los Angeles, CA, USA; VA Greater Los Angeles Healthcare System, Department of Medicine, Los Angeles, CA, USA.
  • Rettig MB; Jonsson Comprehensive Cancer Center, Department of Urology, UCLA, Los Angeles, CA, USA.
  • Witte O; Department of Microbiology, Immunology, and Molecular Genetics at the David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
  • Ryan CJ; Division of Hematology, Oncology, and Transplant, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
  • Fong L; Division of Hematology and Oncology, Department of Medicine, UCSF, San Francisco, CA, USA.
  • Kim W; Division of Hematology and Oncology, Department of Medicine, UCSF, San Francisco, CA, USA.
  • Friedlander T; Division of Hematology and Oncology, Department of Medicine, UCSF, San Francisco, CA, USA.
  • Chou J; Division of Hematology and Oncology, Department of Medicine, UCSF, San Francisco, CA, USA.
  • Li H; Department of Radiation Oncology, UCSF, San Francisco, CA, USA.
  • Das R; Department of Radiation Oncology, UCSF, San Francisco, CA, USA.
  • Li H; Department of Radiation Oncology, UCSF, San Francisco, CA, USA.
  • Moussavi-Baygi R; Department of Radiation Oncology, UCSF, San Francisco, CA, USA.
  • Goodarzi H; Department of Biophysics and Biochemistry, UCSF, San Francisco, CA, USA; Department of Urology, UCSF, San Francisco, CA, USA.
  • Gilbert LA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA; Department of Urology, UCSF, San Francisco, CA, USA.
  • Lara PN; Division of Hematology Oncology, Department of Internal Medicine, University of California Davis, Sacramento, CA, USA; Comprehensive Cancer Center, University of California Davis, Sacramento, CA, USA.
  • Evans CP; Comprehensive Cancer Center, University of California Davis, Sacramento, CA, USA; Department of Urologic Surgery, University of California Davis, Sacramento, CA, USA.
  • Goldstein TC; Division of Hematology and Oncology, Department of Medicine, UCSF, San Francisco, CA, USA; UC Sant Cruz Genome Institute and Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.
  • Stuart JM; UC Sant Cruz Genome Institute and Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.
  • Tomlins SA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Urology, University of Michigan, Ann Arbor, MI, USA.
  • Spratt DE; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
  • Cheetham RK; Illumina, Inc., San Diego, CA, USA.
  • Cheng DT; Illumina, Inc., San Diego, CA, USA.
  • Farh K; Illumina, Inc., San Diego, CA, USA.
  • Gehring JS; Illumina, Inc., San Diego, CA, USA.
  • Hakenberg J; Illumina, Inc., San Diego, CA, USA.
  • Liao A; Illumina, Inc., San Diego, CA, USA.
  • Febbo PG; Illumina, Inc., San Diego, CA, USA.
Cell ; 174(3): 758-769.e9, 2018 07 26.
Article en En | MEDLINE | ID: mdl-30033370
ABSTRACT
While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. Through integrative deep whole-genome and -transcriptome analysis of 101 castration-resistant prostate cancer metastases (109X tumor/38X normal coverage), we identified structural variants altering critical regulators of tumorigenesis and progression not detectable by exome approaches. Notably, we observed amplification of an intergenic enhancer region 624 kb upstream of the androgen receptor (AR) in 81% of patients, correlating with increased AR expression. Tandem duplication hotspots also occur near MYC, in lncRNAs associated with post-translational MYC regulation. Classes of structural variations were linked to distinct DNA repair deficiencies, suggesting their etiology, including associations of CDK12 mutation with tandem duplications, TP53 inactivation with inverted rearrangements and chromothripsis, and BRCA2 inactivation with deletions. Together, these observations provide a comprehensive view of how structural variations affect critical regulators in metastatic prostate cancer.
Asunto(s)
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Variación Estructural del Genoma Límite: Aged / Aged80 / Humans / Male / Middle aged Idioma: En Revista: Cell Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Variación Estructural del Genoma Límite: Aged / Aged80 / Humans / Male / Middle aged Idioma: En Revista: Cell Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos