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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Base Sequence
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Cell Line, Tumor
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Fusion Proteins, bcr-abl / analysis
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Fusion Proteins, bcr-abl / genetics
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Gene Expression Profiling / methods*
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Humans
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
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Male
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Molecular Sequence Data
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Neoplasms / genetics*
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Oncogene Proteins, Fusion / analysis*
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Oncogene Proteins, Fusion / genetics*
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Prostatic Neoplasms / genetics
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Sequence Analysis, DNA / instrumentation
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Sequence Analysis, DNA / methods*
Substances
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MIPOL1-DGKB fusion protein, human
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Oncogene Proteins, Fusion
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SLC45A3-ELK4 fusion protein, human
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TMPRSS2-ERG fusion protein, human
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Fusion Proteins, bcr-abl
Associated data
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GENBANK/FJ423742
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GENBANK/FJ423743
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GENBANK/FJ423744
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GENBANK/FJ423745
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GENBANK/FJ423746
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GENBANK/FJ423747
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GENBANK/FJ423748
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GENBANK/FJ423749
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GENBANK/FJ423750
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GENBANK/FJ423751
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GENBANK/FJ423752
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GENBANK/FJ423753
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GENBANK/FJ423754
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GENBANK/FJ423755