Dataset Information

Chimeric transcript discovery by paired-end transcriptome sequencing.

ABSTRACT: Recurrent gene fusions are a prevalent class of mutations arising from the juxtaposition of 2 distinct regions, which can generate novel functional transcripts that could serve as valuable therapeutic targets in cancer. Therefore, we aim to establish a sensitive, high-throughput methodology to comprehensively catalog functional gene fusions in cancer by evaluating a paired-end transcriptome sequencing strategy. Not only did a paired-end approach provide a greater dynamic range in comparison with single read based approaches, but it clearly distinguished the high-level "driving" gene fusions, such as BCR-ABL1 and TMPRSS2-ERG, from potential lower level "passenger" gene fusions. Also, the comprehensiveness of a paired-end approach enabled the discovery of 12 previously undescribed gene fusions in 4 commonly used cell lines that eluded previous approaches. Using the paired-end transcriptome sequencing approach, we observed read-through mRNA chimeras, tissue-type restricted chimeras, converging transcripts, diverging transcripts, and overlapping mRNA transcripts. Last, we successfully used paired-end transcriptome sequencing to detect previously undescribed ETS gene fusions in prostate tumors. Together, this study establishes a highly specific and sensitive approach for accurately and comprehensively cataloguing chimeras within a sample using paired-end transcriptome sequencing.

SUBMITTER: Maher CA

PROVIDER: S-EPMC2708976 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Chimeric transcript discovery by paired-end transcriptome sequencing.

Maher Christopher A CA Palanisamy Nallasivam N Brenner John C JC Cao Xuhong X Kalyana-Sundaram Shanker S Luo Shujun S Khrebtukova Irina I Barrette Terrence R TR Grasso Catherine C Yu Jindan J Lonigro Robert J RJ Schroth Gary G Kumar-Sinha Chandan C Chinnaiyan Arul M AM

Proceedings of the National Academy of Sciences of the United States of America 20090710 30

Recurrent gene fusions are a prevalent class of mutations arising from the juxtaposition of 2 distinct regions, which can generate novel functional transcripts that could serve as valuable therapeutic targets in cancer. Therefore, we aim to establish a sensitive, high-throughput methodology to comprehensively catalog functional gene fusions in cancer by evaluating a paired-end transcriptome sequencing strategy. Not only did a paired-end approach provide a greater dynamic range in comparison with ...[more]

PMID: 19592507

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Chimeric transcript discovery by paired-end transcriptome sequencing.

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Chimeric transcript discovery by paired-end transcriptome sequencing.

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