Association of germline genetic variants with TMPRSS2-ERG fusion status in prostate cancer

Indu Kohaar*, Qiyuan Li, Yongmei Chen, Lakshmi Ravindranath, Denise Young, Amina Ali, Isabell A. Sesterhenn, Inger L. Rosner, Jennifer Cullen, Shiv Srivastava, Matthew Freedman, Gyorgy Petrovics

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Introduction: Oncogenic activation of ERG resulting from TMPRSS2-ERG gene fusion is a key molecular genetic alteration in prostate cancer (CaP). The frequency of ERG fusion is variable by race; however, there are limited data available on germline polymorphisms associating with ERG fusion status. The goal of this study is to identify the inherited risk variants associating with ERG status of CaP. Materials and Methods: SNP genotyping was performed on the Illumina platform using Infinium Oncoarray SNP chip on blood derived genomic DNA samples from 400 patients treated by radical prostatectomy at a single military institution. ERG status was determined in whole mounted prostate specimens by immuno-histochemistry (IHC) for ERG protein expression. Data analysis approaches included association analyses based on EMMAX and imputation by IMPUTE2. Imputed SNPs were validated by ddPCR. Results: SNP genotyping analysis using imputation identified rs34349373 (p 4.68 × 10-8) and rs2055272 (p 5.62 × 10-8) in TBC1D22B to be significantly associated with ERG fusion status in index tumor and non-index tumor foci. Imputed SNP rs2055272 was further experimentally validated by ddPCR with 98.04% (100/102) concordance. Initial discovery analysis based on SNPs on Oncoarray SNP chip, showed significant (p 10-5) association for SNPs (rs6698333, rs1889877, rs3798999, rs10215144, rs3818136, rs9380660 and rs1792695) with ERG fusion status. The study also replicated two previously known ERG fusion associated SNPs (rs11704416 in chromsome 22; rs16901979 in chromosome 8). Conclusions: This study identified SNPs associated with ERG status of CaP. Impact: The findings may contribute towards defining the underlying genetics of ERG positive and ERG negative CaP patients.

Original languageEnglish
Pages (from-to)1321-1333
Number of pages13
Issue number15
StatePublished - 14 Apr 2020
Externally publishedYes


  • ERG fusion
  • Molecular subtype
  • Prostate cancer
  • SNP


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