title: Poly-gene fusion transcripts and chromothripsis in prostate cancer.
abstract: Complex genome rearrangements are frequently observed in cancer but their impact on tumor molecular biology is largely unknown. Recent studies have identified a new phenomenon involving the simultaneous generation of tens to hundreds of genomic rearrangements, called chromothripsis. To understand the molecular consequences of these events, we sequenced the genomes and transcriptomes of two prostate tumors exhibiting evidence of chromothripsis. We identified several complex fusion transcripts, each containing sequence from three different genes, originating from different parts of the genome. One such poly-gene fusion transcript appeared to be expressed from a chain of small genomic fragments. Furthermore, we detected poly-gene fusion transcripts in the prostate cancer cell line LNCaP, suggesting they may represent a common phenomenon. Finally in one tumor with chromothripsis, we identified multiple mutations in the p53 signaling pathway, expanding on recent work associating aberrant DNA damage response mechanisms with chromothripsis. Overall, our data show that chromothripsis can manifest as massively rearranged transcriptomes. The implication that multigenic changes can give rise to poly-gene fusion transcripts is potentially of great significance to cancer genetics.
authors.affiliation: Vancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Wu
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Wyatt
authors.forename: Andrew
authors.initials: A
authors.lastname: McPherson
authors.forename: Dong
authors.initials: D
authors.lastname: Lin
authors.forename: Brian J
authors.initials: BJ
authors.lastname: McConeghy
authors.forename: Fan
authors.initials: F
authors.lastname: Mo
authors.forename: Robert
authors.initials: R
authors.lastname: Shukin
authors.forename: Anna V
authors.initials: AV
authors.lastname: Lapuk
authors.forename: Steven J M
authors.initials: SJ
authors.lastname: Jones
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gleave
authors.forename: Stanislav V
authors.initials: SV
authors.lastname: Volik
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Wang
authors.forename: S Cenk
authors.initials: SC
authors.lastname: Sahinalp
authors.forename: Colin C
authors.initials: CC
authors.lastname: Collins
mesh_terms: D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D050939:Gene Fusion; D006801:Humans; D008297:Male; D009154:Mutation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology