%0 Journal Article %1 Maher:2009:Proc-Natl-Acad-Sci-U-S-A:19592507 %A Maher, C A %A Palanisamy, N %A Brenner, J C %A Cao, X %A Kalyana-Sundaram, S %A Luo, S %A Khrebtukova, I %A Barrette, T R %A Grasso, C %A Yu, J %A Lonigro, R J %A Schroth, G %A Kumar-Sinha, C %A Chinnaiyan, A M %D 2009 %J Proc Natl Acad Sci U S A %K cancer rna-seq %N 30 %P 12353-12358 %R 10.1073/pnas.0904720106 %T Chimeric transcript discovery by paired-end transcriptome sequencing %U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2708976/ %V 106 %X 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.

@article{Maher:2009:Proc-Natl-Acad-Sci-U-S-A:19592507, 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.}, added-at = {2017-05-10T23:21:07.000+0200}, author = {Maher, C A and Palanisamy, N and Brenner, J C and Cao, X and Kalyana-Sundaram, S and Luo, S and Khrebtukova, I and Barrette, T R and Grasso, C and Yu, J and Lonigro, R J and Schroth, G and Kumar-Sinha, C and Chinnaiyan, A M}, biburl = {https://www.bibsonomy.org/bibtex/27016215bc3df736599e400b1dda9707d/marcsaric}, description = {Chimeric transcript discovery by paired-end transcriptome sequencing}, doi = {10.1073/pnas.0904720106}, interhash = {ba456c5ee8cb7416279bd57b14d04306}, intrahash = {7016215bc3df736599e400b1dda9707d}, journal = {Proc Natl Acad Sci U S A}, keywords = {cancer rna-seq}, month = jul, number = 30, pages = {12353-12358}, pmid = {19592507}, timestamp = {2017-05-10T23:21:07.000+0200}, title = {Chimeric transcript discovery by paired-end transcriptome sequencing}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2708976/}, volume = 106, year = 2009 }