title: Novel fusion transcripts associate with progressive prostate cancer.
abstract: The mechanisms underlying the potential for aggressive behavior of prostate cancer (PCa) remain elusive. In this study, whole genome and/or transcriptome sequencing was performed on 19 specimens of PCa, matched adjacent benign prostate tissues, matched blood specimens, and organ donor prostates. A set of novel fusion transcripts was discovered in PCa. Eight of these fusion transcripts were validated through multiple approaches. The occurrence of these fusion transcripts was then analyzed in 289 prostate samples from three institutes, with clinical follow-up ranging from 1 to 15 years. The analyses indicated that most patients [69 (91%) of 76] positive for any of these fusion transcripts (TRMT11-GRIK2, SLC45A2-AMACR, MTOR-TP53BP1, LRRC59-FLJ60017, TMEM135-CCDC67, KDM4-AC011523.2, MAN2A1-FER, and CCNH-C5orf30) experienced PCa recurrence, metastases, and/or PCa-specific death after radical prostatectomy. These outcomes occurred in only 37% (58/157) of patients without carrying those fusion transcripts. Three fusion transcripts occurred exclusively in PCa samples from patients who experienced recurrence or PCaerelated death. The formation of these fusion transcripts may be the result of genome recombination. A combination of these fusion transcripts in PCa with Gleason's grading or with nomogram significantly improves the prediction rate of PCa recurrence. Our analyses suggest that formation of these fusion transcripts may underlie the aggressive behavior of PCa.
authors.forename: Yan P
authors.initials: YP
authors.lastname: Yu
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.forename: Zhanghui
authors.initials: Z
authors.lastname: Chen
authors.forename: Silvia
authors.initials: S
authors.lastname: Liu
authors.forename: Amantha
authors.initials: A
authors.lastname: Michalopoulos
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Zulfiqar G
authors.initials: ZG
authors.lastname: Gulzar
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Cieply
authors.forename: Alyssa
authors.initials: A
authors.lastname: Luvison
authors.forename: Bao-Guo
authors.initials: BG
authors.lastname: Ren
authors.forename: James D
authors.initials: JD
authors.lastname: Brooks
authors.forename: David
authors.initials: D
authors.lastname: Jarrard
authors.forename: Joel B
authors.initials: JB
authors.lastname: Nelson
authors.forename: George K
authors.initials: GK
authors.lastname: Michalopoulos
authors.forename: George C
authors.initials: GC
authors.lastname: Tseng
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Luo
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005500:Follow-Up Studies; D050939:Gene Fusion; D015723:Gene Library; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011467:Prostate / Q000473:pathology; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D059467:Transcriptome; D055815:Young Adult
chemical_list: D012333:RNA, Messenger