title: Transcriptome sequencing to detect gene fusions in cancer.
abstract: Recurrent gene fusions, typically associated with haematological malignancies and rare bone and soft-tissue tumours, have recently been described in common solid tumours. Here we use an integrative analysis of high-throughput long- and short-read transcriptome sequencing of cancer cells to discover novel gene fusions. As a proof of concept, we successfully used integrative transcriptome sequencing to 're-discover' the BCR-ABL1 (ref. 10) gene fusion in a chronic myelogenous leukaemia cell line and the TMPRSS2-ERG gene fusion in a prostate cancer cell line and tissues. Additionally, we nominated, and experimentally validated, novel gene fusions resulting in chimaeric transcripts in cancer cell lines and tumours. Taken together, this study establishes a robust pipeline for the discovery of novel gene chimaeras using high-throughput sequencing, opening up an important class of cancer-related mutations for comprehensive characterization.
authors.affiliation: Michigan Center for Translational Pathology, Ann Arbor, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Maher
authors.forename: Chandan
authors.initials: C
authors.lastname: Kumar-Sinha
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cao
authors.forename: Shanker
authors.initials: S
authors.lastname: Kalyana-Sundaram
authors.forename: Bo
authors.initials: B
authors.lastname: Han
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Jing
authors.forename: Lee
authors.initials: L
authors.lastname: Sam
authors.forename: Terrence
authors.initials: T
authors.lastname: Barrette
authors.forename: Nallasivam
authors.initials: N
authors.lastname: Palanisamy
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D016044:Fusion Proteins, bcr-abl / Q000032:analysis / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000295:instrumentation / Q000379:methods*
chemical_list: C540012:MIPOL1-DGKB fusion protein, human; D015514:Oncogene Proteins, Fusion; C540011:SLC45A3-ELK4 fusion protein, human; C515553:TMPRSS2-ERG fusion protein, human; D016044:Fusion Proteins, bcr-abl