Identifying the Molecular Mechanisms of Prostate Tumorigenesis Associated with Multigenic 3p13-14 Locus Loss Using a Novel CRISPR-Organoid Platform

Abstract

Human prostate cancers can feature chromosome-scale alterations, but it remains challenging to determine the causal relationship between these alterations and cancer formation. We established a mouse primary prostate organoid platform to model the large 3p13-14 locus deletion, which typically spans six genes and occurs in 15~20 of prostate cancer patients. We performed multi-omics analysis to study the role of Foxp1, a putative tumor suppressor from this region. To model the loss of the entire locus, we developed a CRISPR editing approach to efficiently generate the large deletions through a single step. We are continuing the analysis of the multi-omics data and the in vivo transplantation of the organoids carrying the desired deletions. Together, our study will provide both mechanistic insight and a comprehensive view about the putative tumor suppressor locus and serve as a paradigm for studying other frequent chromosomal alterations in prostate cancer.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2020
Accession Number
AD1108305

Entities

People

  • Weiran Feng

Organizations

  • Sloan-Kettering Institute

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Androgen Receptors
  • Biology
  • Biomedical Research
  • Cancer
  • Cells
  • Chromosome Structures
  • Gene Expression
  • Genes
  • Genetic Phenomena
  • Genetics
  • Medical Personnel
  • Neoplasms
  • Organoids
  • Personnel Management
  • Platforms
  • Prostate
  • Prostate Cancer
  • Public Health
  • Suppressors
  • Therapy
  • Training
  • Transplantation

Fields of Study

  • Biology

Readers

  • Molecular and genetic basis of cancer.
  • Systems Analysis and Design

Technology Areas

  • Biotechnology