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Sep 10, 2015
 |  BC Innovations  |  Tools & Techniques

Undiscovered country

NuGen Technologies' RNA sequencing method finds rare cancer gene fusions

Although total RNA sequencing can identify oncogenes caused by the fusion of two genes, the method is inefficient and costly because the transcripts from the abnormal genes are often rare. NuGen Technologies Inc. has developed an efficient sequencing technique that can find rare transcripts from fused genes, and can help clinicians identify driver mutations in cancer that might be missed with total RNA sequencing.

Douglas Amorese, VP of R&D at NuGen, said, "Conventional RNA sequencing requires 125 million reads in order to detect a particular gene fusion, and yet with our technology we are able to see gene fusions much more easily with many fewer reads."

Amorese said gene fusions such as the BCR-ABL tyrosine kinase oncogene are well known drivers of cancer and are transcribed at levels that can be picked up frequently by conventional RNA sequencing (RNA-Seq), but many transcripts from other gene rearrangements are harder to find.

"The levels of expression of these fusions are really hard to anticipate, but they tend to be expressed at very low levels and that is why it is difficult to pick them up using RNA sequencing," Amorese said.

He said the gene fusion events are typically the result of a translocation where a portion of one chromosome is rearranged into another chromosome. Amorese said when the rearrangements occur within introns, the resulting fused genes can be transcribed, spliced into productive mRNAs and translated into abnormal proteins.

NuGen's method for detecting transcripts from gene fusions, dubbed Single Primer Enrichment Technology (SPET), can detect abnormal transcripts with about 80-fold fewer reads because it targets genes that have been previously associated with cancer-driving chromosomal rearrangements.

Amorese told BioCentury the company performed in-house studies to show the technique could detect gene fusion transcripts that other technologies missed. SPET identified gene fusion transcripts from cancer cells that were not found in 125 million sequencing reads using Illumina Inc.'s standard RNA-Seq platform.

In a July study published in PLoS One, NuGen showed the SPET method, which targeted over 400 genes, identified rare gene fusions more efficiently than Illumina's deeper RNA sequencing. (See Figure: Finding fusions)

Illumina's method uses a whole transcriptome library and is not biased to any...

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