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Comprehensive molecular characterization of urothelial bladder carcinoma.

Publication ,  Journal Article
Cancer Genome Atlas Research Network,
Published in: Nature
March 20, 2014

Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomas to provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3-TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.

Duke Scholars

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

March 20, 2014

Volume

507

Issue

7492

Start / End Page

315 / 322

Location

England

Related Subject Headings

  • Virus Integration
  • Urinary Bladder Neoplasms
  • TOR Serine-Threonine Kinases
  • Signal Transduction
  • RNA, Messenger
  • Proto-Oncogene Proteins c-akt
  • Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • Oxidative Stress
  • Molecular Targeted Therapy
 

Citation

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Cancer Genome Atlas Research Network, . (2014). Comprehensive molecular characterization of urothelial bladder carcinoma. Nature, 507(7492), 315–322. https://doi.org/10.1038/nature12965
Cancer Genome Atlas Research Network, A. J. “Comprehensive molecular characterization of urothelial bladder carcinoma.Nature 507, no. 7492 (March 20, 2014): 315–22. https://doi.org/10.1038/nature12965.
Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014 Mar 20;507(7492):315–22.
Cancer Genome Atlas Research Network, A. J. “Comprehensive molecular characterization of urothelial bladder carcinoma.Nature, vol. 507, no. 7492, Mar. 2014, pp. 315–22. Pubmed, doi:10.1038/nature12965.
Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014 Mar 20;507(7492):315–322.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

March 20, 2014

Volume

507

Issue

7492

Start / End Page

315 / 322

Location

England

Related Subject Headings

  • Virus Integration
  • Urinary Bladder Neoplasms
  • TOR Serine-Threonine Kinases
  • Signal Transduction
  • RNA, Messenger
  • Proto-Oncogene Proteins c-akt
  • Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • Oxidative Stress
  • Molecular Targeted Therapy