Multiplex Functional Interrogation of Oncogenic Networks in Bladder Cancer

Abstract

We have developed and characterized a new methodology to generate genotypically and phenotypically diverse mouse models of bladder cancer that may better reflect the heterogeneity of the human disease. We have introduced lentiviral pools encoding gain- and loss-of-function events associated with bladder cancer in multiplexed fashion in the context of a mouse bladder urothelial transformation assay. This led to the generation of multiple tumors models that are polyclonal and exhibit multiple histologies including typical urothelial carcinoma, papillary urothelial carcinoma, squamous cell carcinoma, and sarcomatoid carcinoma. Furthermore, transcriptional profiling studies and the application of published molecular classifiers indicate that these tumors reflect multiple molecular subtypes of bladder cancer. This methodology and the resultant tumor models may be a valuable resource for the field in understanding the interactions of oncogenic events in tumorigenesis and investigating therapeutic strategies in bladder cancer.

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Document Details

Document Type
Technical Report
Publication Date
Nov 01, 2022
Accession Number
AD1199174

Entities

People

  • John K Lee

Organizations

  • Fred Hutchinson Cancer Center

Tags

DTIC Thesaurus Topics

  • Biology
  • Biomedical Research
  • Bladder Cancer
  • Cancer
  • Carcinoma
  • Cells
  • Chemical Reactions
  • Computational Science
  • Data Analysis
  • Demographic Cohorts
  • Genetic Phenomena
  • Genetics
  • Genomics
  • Histology
  • Interrogation
  • Machine Learning
  • Medical Personnel
  • Neoplasms
  • Organoids
  • Polymerase Chain Reaction
  • United States

Fields of Study

  • Medicine

Readers

  • Molecular Biology and Genetics
  • Oncology