Abstract

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.

Details

Title
Mutant allele quantification reveals a genetic basis for TP53 mutation-driven castration resistance in prostate cancer cells
Author
Lei, Kefeng 1 ; Sun, Ran 2 ; Chen, Lee H 3 ; Diplas, Bill H 3   VIAFID ORCID Logo  ; Moure, Casey J 3 ; Wang, Wenzhe 4   VIAFID ORCID Logo  ; Hansen, Landon J 3 ; Tao, Yulei 5 ; Chen, Xufeng 5 ; Chin-Pu, Jason Chen 3 ; Greer, Paula K 3 ; Zhao, Fangping 6 ; Yan, Hai 3 ; Bigner, Darell D 3 ; Huang, Jiaoti 5 ; He, Yiping 3 

1  Department of Pathology, Duke University Medical Center, Durham, NC, USA; The Preston Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA; General Surgery, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Zhejiang, China 
2  Department of Pathology, Duke University Medical Center, Durham, NC, USA; The Preston Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA; Scientific Research Center, China-Japan Union Hospital, Jilin University, Jilin, China 
3  Department of Pathology, Duke University Medical Center, Durham, NC, USA; The Preston Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA 
4  Department of Pathology, Duke University Medical Center, Durham, NC, USA; The Preston Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA; Center for Molecular Medicine, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China 
5  Department of Pathology, Duke University Medical Center, Durham, NC, USA 
6  Genetron Health, Durham, NC, USA 
Pages
1-10
Publication year
2018
Publication date
Aug 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-30062-z
ProQuest document ID
2091208267
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.