Coordinated Roles of SPOP Mutation and CHD1 Deletion in Prostate Cancer Pathogenesis
Abstract
SPOP mutations occur in 6-15% of cases of prostate cancer (PCa). SPOP mutations are early events that have been found in localized and metastatic stages of PCa but, have shown to be a poor biomarker for risk stratification in patients. Homozygous deletion of CHD1 is the most common recurrent alteration that occurs mostly in the SPOP mutant subclass. CHD1 loss is commonly subclonal, occurs in 5-10% of cases in PCa, 80% of which belong to the mutant SPOP subclass. Tumors carrying combined SPOP mutant; CHD1 loss have distinct gene expression patterns, DNA hypermethylation and highest AR activity compared to other subtypes of PCa. Despite the discovery of this subtype in 2012, molecular mechanisms driving pathogenesis remain to be understood. This stem, in part, from the lack of relevant model systems harboring these specific genetic alterations for use as study tools. Herein, we describe unique genetically engineered mouse models, 3D organoid systems and cell lines that have been developed and deployed in our laboratory to recapitulate clinically observed genotypes in normal prostate cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2018
- Accession Number
- AD1063801
Entities
People
- Kaveri Arora
Organizations
- Weill Cornell Medicine