Association of germline genetic variants with <i>TMPRSS2-ERG</i> fusion status in prostate cancer.
Abstact
Oncogenic activation of ERG resulting from <i>TMPRSS2-ERG</i> 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.
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.
SNP genotyping analysis using imputation identified rs34349373 (p 4.68 × 10 <sup><b>-8</b></sup> ) and rs2055272 (p 5.62 × 10<sup>-8</sup>) in <i>TBC1D22B</i> 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<sup>-5</sup>) 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).
This study identified SNPs associated with ERG status of CaP.
The findings may contribute towards defining the underlying genetics of ERG positive and ERG negative CaP patients.
Authors
- Ali A
- Chen Y
- Cullen J
- Freedman M
- Kohaar I
- Li Q
- Petrovics G
- Ravindranath L
- Rosner IL
- Sesterhenn IA
- Srivastava S
- Young D