- 日本人前立腺でもTMPRSS2:ERG gene fusion は結構な頻度で認められるのだと評価できる。
ETS family-associated gene fusions in Japanese prostate cancer: analysis of 194 radical prostatectomy samples.
Miyagi Y, Sasaki T, Fujinami K, Sano J, Senga Y, Miura T, Kameda Y, Sakuma Y, Nakamura Y, Harada M, Tsuchiya E.
Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan. firstname.lastname@example.org
- 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 reverse-transcriptase 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 ≤7 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' fusion partners for the ETS genes, we performed 5' RACE using fresh-frozen prostate cancer samples. We identified only the normal 5' 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.
Prostate. 2011 Apr;71(5):489-97.
TMPRSS2-ERG gene fusion prevalence and class are significantly different in prostate cancer of Caucasian, African-American and Japanese patients.
Magi-Galluzzi C, Tsusuki T, Elson P, Simmerman K, LaFargue C, Esgueva R, Klein E, Rubin MA, Zhou M.
Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Prostate cancer (PCa) exhibits significant differences in prevalence and mortality among different ethnic groups. The underlying genetics is not well understood. TMPRSS2-ERG fusion is a common recurrent chromosomal aberration in PCa and is however not studied among different ethnic groups. We examined the prevalence and class of TMPRSS2-ERG gene fusion in PCa from Caucasian, African-American, and Japanese patients.
MATERIALS AND METHODS:
A tissue microarray of PCa from 42 Caucasians, 64 African-Americans, and 44 Japanese patients who underwent radical prostatectomies (RP) was studied for TMPRSS2-ERG fusion using a multicolor interphase fluorescence in situ hybridization assay for ERG gene break-apart.
TMPRSS2-ERG gene fusion was present in 50% (21/42) of Caucasians, 31.3% (20/64) of African-Americans, and 15.9% (7/44) of Japanese (P=0.003). The gene fusion through translocation, deletion, or both occurred in 61.9% (13/21), 38.1% (8/21), and 0% (0/21) in Caucasians, 20% (4/20), 60% (12/20), and 20% (4/20) in African-Americans, and 71.4% (5/7), 28.6% (2/7), and 0% (0/7) in Japanese patients (P=0.02). A multivariate analysis demonstrated that TMPRSS2-ERG gene fusion correlated with the ethnicity (P=0.03), marginally correlated with the pathologic stage (P=0.06), but not other clinicopathologic parameters, including age, preoperative PSA levels, and Gleason score.
The prevalence and class of TMPRSS2-ERG are significantly different in PCa of Caucasian, African-American, and Japanese patients. Future studies of the molecular pathways implicated in TMPRSS2-ERG gene fusion may shed light on the disparity in prevalence and mortality of PCa among different ethnic groups and help design better prevention and treatment strategies.