Journal
NATURE
Volume 458, Issue 7234, Pages 97-U9Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature07638
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Funding
- National Institutes of Health
- Department of Defense
- Early Detection Research Network
- NCIBI [U54 DA 021519]
- American Association of Cancer Research Amgen Fellowship in Clinical/Translational Research
- Canary Foundation and American Cancer Society Early Detection Postdoctoral Fellowship
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Recurrent gene fusions, typically associated with haematological malignancies and rare bone and soft-tissue tumours(1), have recently been described in common solid tumours(2-9). 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(2,3) 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.
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