Mutant allele quantification reveals a genetic basis for TP53 mutation-driven castration resistance in prostate cancer cells.

Journal Article (Journal Article)

The concept that human cancer is in essence a genetic disease driven by gene mutations has been well established, yet its utilization in functional studies of cancer genes has not been fully explored. Here, we describe a simple genetics-based approach that can quickly and sensitively reveal the effect of the alteration of a gene of interest on the fate of its host cells within a heterogeneous population, essentially monitoring the genetic selection that is associated with and powers the tumorigenesis. Using this approach, we discovered that loss-of-function of TP53 can promote the development of resistance of castration in prostate cancer cells via both transiently potentiating androgen-independent cell growth and facilitating the occurrence of genome instability. The study thus reveals a novel genetic basis underlying the development of castration resistance in prostate cancer cells and provides a facile genetic approach for studying a cancer gene of interest in versatile experimental conditions.

Full Text

Duke Authors

Cited Authors

  • Lei, K; Sun, R; Chen, LH; Diplas, BH; Moure, CJ; Wang, W; Hansen, LJ; Tao, Y; Chen, X; Chen, C-PJ; Greer, PK; Zhao, F; Yan, H; Bigner, DD; Huang, J; He, Y

Published Date

  • August 21, 2018

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • 12507 -

PubMed ID

  • 30131529

Pubmed Central ID

  • PMC6104024

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/s41598-018-30062-z


  • eng

Conference Location

  • England