title: 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 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.
authors.affiliation: Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan. miyagi@gancen.asahi.yokohama.jp
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Fujinami
authors.forename: Jinyu
authors.initials: J
authors.lastname: Sano
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Senga
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miura
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kameda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sakuma
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Masaoki
authors.initials: M
authors.lastname: Harada
authors.forename: Eiju
authors.initials: E
authors.lastname: Tsuchiya
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D005838:Genotype; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D016612:Paraffin Embedding; D010641:Phenotype; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016707:Tissue Fixation; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000071230:Transcriptional Regulator ERG
chemical_list: D004268:DNA-Binding Proteins; C072312:ERG protein, human; C095239:ETV1 protein, human; C086680:ETV5 protein, human; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; C540011:SLC45A3-ELK4 fusion protein, human; C515553:TMPRSS2-ERG fusion protein, human; C529661:TMPRSS2-ETV1 fusion protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; C439768:hnRNP A2; D017430:Prostate-Specific Antigen