Until recently, chromosomal translocations and fusion genes have been an underappreciated class of mutations in solid tumors. Next-generation sequencing technologies provide an opportunity for systematic characterization of cancer cell transcriptomes, including the discovery of expressed fusion genes resulting from underlying genomic rearrangements.
Using paired-end RNA-seq and improved bioinformatic stratification, researchers at the Institute for Molecular Medicine Finland have discovered a number of novel fusion genes in breast cancer, and identified VAPB-IKZF3 as a potential fusion gene with importance for the growth and survival of breast cancer cells1.
Researchers at Genentech performed single-end RNA-Seq on human prostate adenocarcinoma samples and their corresponding normal tissues, and developed bioinformatics methods to specifically identify transcription-induced chimeras (TICs), a type of gene fusion2. Both prostate and reference samples exhibit a wide range of TIC events and some TIC events, such as MSMB-NCOA4, may play functional roles in cancer.
Deep transcriptional analysis with either single-end or paired-end RNA sequencing can effectively identify gene fusions across the genome.
1. Edgren H, Murumaegi A, Kangaspeska S, Nicorici D, Hongisto V, Kleivi K, Rye IH, Nyberg S, Wolf M, Boerresen-Dale AL, Kallioniemi O. (2011) Identification of fusion genes in breast cancer by paired-end RNA-sequencing. Genome Biol 12(1), R6. [abstract]
2. Nacu S, Yuan W, Kan Z, Bhatt D, Rivers CS, Stinson J, Peters BA, Modrusan Z, Jung K, Seshagiri S, Wu TD. (2011) Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples. BMC Med Genomics 4(1), 11. [abstract]
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