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Nature. 2009 Mar 5;458(7234):97-101. doi: 10.1038/nature07638. Epub 2009 Jan 11.

Transcriptome sequencing to detect gene fusions in cancer.

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  • 1Michigan Center for Translational Pathology, Ann Arbor, USA.

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.

PMID:
19136943
[PubMed - indexed for MEDLINE]
PMCID:
PMC2725402
Free PMC Article
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