Proceedings of the National Academy of Sciences - PNAS, 2009-07, Vol.106 (30), p.12353-12358
2009
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- Autor(en) / Beteiligte
- Titel
- Chimeric transcript discovery by paired-end transcriptome sequencing
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2009-07, Vol.106 (30), p.12353-12358
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2009
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.0904720106Titel-ID: cdi_jstor_primary_40484140
- Format
- –
- Schlagworte
- Base Sequence, Biological Sciences, Breast cancer, Cell Line, Tumor, Cell lines, Cells, Chimeras, Chromosomes, Exons, Fusion Proteins, bcr-abl - genetics, Gene Expression Profiling - methods, Gene Expression Regulation, Neoplastic, Gene fusion, Genes, Genomes, Humans, K562 Cells, Male, Molecular Sequence Data, Mutation, Neoplasms - genetics, Neoplasms - pathology, Oncogene Proteins, Fusion - genetics, Prostate cancer, Prostatic Neoplasms - genetics, Prostatic Neoplasms - pathology, Reverse Transcriptase Polymerase Chain Reaction, Ribonucleic acid, RNA, RNA, Messenger - genetics, RNA, Messenger - metabolism, Sequence Analysis, DNA, Sequencing, Studies, Transcription, Genetic, Tumors