Oncotarget Association of germline genetic variants with TMPRSS2-ERG fusion status

Oncotarget Volume 11 Issue 15 reported that the frequency of ERG fusion is variable by race; however, there is limited data available on germline polymorphisms associated with ERG fusion status.

Initial discovery analysis based on SNPs on an Oncoarray SNP chip, showed significant association for SNPs with ERG fusion status.

This study identified SNPs associated with ERG status of Ca P. The findings may contribute towards defining the underlying genetics of ERG positive and ERG negative Ca P patients.

Dr. Indu Kohaar and Dr. Gyorgy Petrovics from The Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, Maryland, USA as well as The Henry Jackson Foundation for the Advancement of Military Medicine (HJF), Bethesda, Maryland, USA said, "Prostate cancer (CaP) is a major cause of morbidity and mortality worldwide."

"Prostate cancer (CaP) is a major cause of morbidity and mortality worldwide."

- Dr. Indu Kohaar & Dr. Gyorgy Petrovics - The Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, the Walter Reed National Military Medical Center, and The Henry Jackson Foundation for the Advancement of Military Medicine (HJF)

Key biological differences are evident across ERG fusion status , including distinct methylation patterns, with hypermethylation more pronounced in ERG positive versus negative Ca P tumors.

In addition, the processes of tumor evolution are also different between fusion positive and negative tumors, with TMPRSS2-ERG tumors characterized by chromoplexy, while chromothripsis is more common in TMPRSS2-ERG negative tumors.

Considering the multiclonal and heterogenous nature of Ca P, it is important to examine all tumor foci for ERG fusion status as any of these may lead to aggressive Ca P.

Figure 1: Schematic representation of the study.

Thus, it is hypothesized that ERG gene fusion status of AA and CA patients reflects underlying biological and/or genetic differences of Ca P development.

Since TMPRSS2-ERG fusion is considered to be an early event in Ca P, it is anticipated that SNPs associated with Ca P risk may influence ERG fusion status.

The Kohaar/Petrovics Research Team concluded in their Oncotarget Research Paper "this study identified the association of 2 SNPs (rs34349373 and rs2055272) in TBC1D22B with ERG fusion status where the minor alleles are associated with an ERG negative subtype of CaP. Additionally, rs3798999 SNP (ADGRB3) was significantly associated with the development of BCR in ERG negative patient cohort. Validation study in independent large patient cohort with race stratified analysis, and functional understanding of the biology of these SNPs in relation to ERG phenotype are warranted. Overall, this study may contribute toward defining the underlying biology and genetics of ERG positive and ERG negative CaP in AA and CA patients."

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DOI - https://doi.org/10.18632/oncotarget.27534

Full text - https://www.oncotarget.com/article/27534/text/

Correspondence to - Indu Kohaar - ikohaar@cpdr.org and Gyorgy Petrovics - gpetrovics@cpdr.org

Keywords - prostate cancer, TMPRSS2-ERG, molecular subtype, ERG fusion, SNP

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