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Transcriptome sequencing to detect gene fusions in cancer.

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.

SUBMITTER: Maher CA

PROVIDER: S-EPMC2725402 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Transcriptome sequencing to detect gene fusions in cancer.

Maher Christopher A CA 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

Nature 20090111 7234

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 an ...[more]

PMID: 19136943

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