ETS family-associated gene fusions in Japanese prostate cancer: analysis of 194 radical prostatectomy samples

Abstract

The incidence and clinical significance of the TMPRSS2:ERG gene fusion in prostate cancer has been investigated with contradictory results. It is now common knowledge that significant variability in gene alterations exists according to ethnic background in various kinds of cancer. In this study, we evaluated gene fusions involving the ETS gene family in Japanese prostate cancer. Total RNA from 194 formalin-fixed and paraffin-embedded prostate cancer samples obtained by radical prostatectomy was subjected to reversetranscriptase polymerase chain reaction to detect the common TMPRSS2:ERG T1-E4 and T1-E5 fusion transcripts and five other non-TMPRSS2:ERG fusion transcripts. We identified 54 TMPRSS2:ERG-positive cases (54/194, 28%) and two HNRPA2B1:ETV1-positive cases (2/194, 1%). The SLC45A3-ELK4 transcript, a fusion transcript without structural gene rearrangement, was detectable in five cases (5/194, 3%). The frequencies of both TMPRSS2:ERG-and non-TMPRSS2:ERG-positive cases were lower than those reported for European, North American or Brazilian patients. Internodular heterogeneity of TMPRSS2:ERG was observed in 5 out of 11 multifocal cases (45%); a frequency similar to that found in European and North American cases. We found a positive correlation between the TMPRSS2:ERG fusion and a Gleason score of r7 and patient age, but found no relationship with pT stage or plasma prostate-specific antigen concentration. To exclude the possibility that Japanese prostate cancer displays novel TMPRSS2:ERG transcript variants or has unique 5 0 fusion partners for the ETS genes, we performed 5 0 RACE using fresh-frozen prostate cancer samples. We identified only the normal 5 0 cDNA ends for ERG, ETV1 and ETV5 in fusion-negative cases. Because we identified a relatively low frequency of TMPRSS2:ERG and other fusions, further evaluation is required before this promising molecular marker should be introduced into the management of Japanese prostate cancer patients.

A Prospective Investigation of PTEN Loss and ERG Expression in Lethal Prostate Cancer

“…Importantly, the association of PTEN loss with lethal events among ERG fusion-negative tumors was much stronger than that seen for PTEN loss considered without ERG status, and this association remained strong even when considering tumors with heterogeneous PTEN loss. Finally, white men primarily comprise our cohort (97%), so our results may not be generalizable to other racial/ethnic groups, in which ERG expression and PTEN loss may be less frequent (45)(46)(47)(48)(49)(50).…”

TMPRSS2-ERG gene fusion in Turkish patients with localized prostate cancer: results of radical prostatectomy specimens

“…The patients from United States and Europe have displayed much higher fusion rates (50%-70%) relative to Asian countries (15.9-29.7%) such as China, Korea, Malaysia, Japan and India. [11,[22][23][24][25][26] To date, no study has evaluated the frequency of TMPRSS2-ERG gene fusion in patients with prostate cancer in Turkish population. As a first and unique study, we evaluated the patients with localized cancer who had undergone radical retropubic prostatectomy to determine the exact l status of TMPRSS2-ERG gene fusion.…”

“…[6] The fusion of TMPRSS2 and ERG seems to be specific for prostate cancer. [7] The results of prevalence studies from different countries have shown some discrepancy [8][9][10][11][12] which might be attributed to genetic variations between nations. [13] Many studies have been conducted to evaluate the fusion of these genes in different subtypes of prostate cancer to detect their importance in predicting aggressive forms.…”

Prostate cancer research in China

“…13 Such findings are consistent with previous reports on PCa patients in China, 14 as well as those in Japanese and Korean populations. [15][16][17] Two novel gene fusions, CTAGE5-KHDRBS3 and USP9Y-TTTY15, occurred frequently in our patient cohort; 13 further validation in a larger and multicentre population is warranted. These differences may be further utilized in exploring the unique Chinese mechanism upon tumour onset and progression, as a study has confirmed a possible alternative path of carcinogenesis in gene fusion and PTEN inactivation.…”