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