Multiplex Functional Interrogation of Combinations of Genetic Alterations in Prostate Cancer

Abstract

During the grant period, we have developed a higher-order, combinatorial genetics strategy using lentiviral (LV) libraries of cancer-associated genetic events introduced into benign epithelial cells that are subsequently engrafted in vivo for tumorigenic selection. We have generated several tumors using this approach that demonstrate clinically relevant, mixed cancer histologies. We incorporated massively parallel single-cell LV barcode sequencing to identify genetic alterations that contribute to the diverse phenotypes represented in the tumors. Validation of the findings is currently ongoing. These initial studies provide proof-of-principle of this powerful approach to rapidly investigate genotype-phenotype relationships in cancer initiation starting from primary epithelial cells. Our ultimate goal is to generate genetically defined models of prostate cancer that recapitulate the diversity of human prostate cancer.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2022
Accession Number
AD1191478

Entities

People

  • Shan Li

Organizations

  • Fred Hutchinson Cancer Center

Tags

DTIC Thesaurus Topics

  • Acquisition
  • Biomedical Research
  • Bladder Cancer
  • Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Covid-19
  • Epithelial Cells
  • Genes
  • Genetics
  • Giant Cells
  • Neoplasms
  • Phenotypes
  • Prostate
  • Prostate Cancer
  • Tissues

Fields of Study

  • Biology

Readers

  • Computational Fluid Dynamics (CFD)
  • Molecular and Cellular Biology
  • Oncology (Cancer Research).

Technology Areas

  • Biotechnology