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Transcriptome Sequencing to Detect Gene Fusions in Cancer
Maher CA, Kumar-Sinha C, Cao X, Kalyana-Sundaram S, Han B, Jing X, Sam L, Barrette T, Palanisamy N, Chinnaiyan AM.
Nature. 2009 Mar 5;458(7234):97-101. Epub 2009 Jan 11.
Editor's Summary
http://www.nature.com/nature/journal/v458/n7234/edsumm/e090305-12.html
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 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.
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