Transcriptome sequencing to detect gene fusions in cancer.
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.
Maher
Christopher A
CA
Michigan Center for Translational Pathology, Ann Arbor, USA.
Kumar-Sinha
Chandan
C
Cao
Xuhong
X
Kalyana-Sundaram
Shanker
S
Han
Bo
B
Jing
Xiaojun
X
Sam
Lee
L
Barrette
Terrence
T
Palanisamy
Nallasivam
N
Chinnaiyan
Arul M
AM
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*
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