Caris’ whole transcriptome sequencing (WTS) uses the capabilities of high-throughput sequencing to gain insight into the RNA profiles of patient tumors. WTS provides extremely broad coverage and strong resolution (depth) into the dynamic nature of the transcriptome.
WTS enables gene fusion detection and RNA splice variant detection all from one streamlined test. The test identifies fusions independent of the breakpoints in DNA and has the ability to detect rare, or novel, fusion events better than targeted RNA sequencing or DNA-based methods. By providing broad exon coverage and capturing essentially all possible fusion partners, whole transcriptome sequencing can reliably detect different types of gene fusions, while reducing false positives caused by non-expressed rearrangements.
|Genes covered||Essentially All (~22k) genes; Clinically actionable genes will be highlighted on Caris Reports and unclassified RNA alterations will be available separately|
|Reads/Sample||23M read count|
|Assay method||Hybrid capture|
Figure 1: Sample Circos plot of various clinical fusions
With Whole Exome Sequencing (WES), Whole Transcriptome Sequencing (WTS), extensive proteomic testing services, and advanced machine-learning capabilities, Caris molecular profiling is the most comprehensive and clinically relevant molecular profile for cancer patients in the industry.
|Fusion Analysis Method||# of Genes||Clinical Actionability||Fusion Expression|
|MI Transcriptome||Essentially all genes||Can detect gene fusions||Can identify if fusion is expressed|
|DNA Sequencing||Limited (hot spots)||Can detect rearrangements that may not always result in gene fusions||Cannot identify if fusion is expressed|
Figure 2: Diagram showing advantages of MI Transcriptome over DNA Sequencing for fusion analysis
Example: An ALK fusion may be found at the DNA level but it may not be expressed as RNA. Some fusion partners such as EML4 result in dramatic overexpression of ALK and increase in its kinase signaling. However, other fusion partners may not result in ALK overexpression and thus would not potentiate the oncogenic ALK kinase activity. Such cases are unlikely to derive significant benefit from targeted ALK therapy.
RNA-based analysis, via Whole Transcriptome Sequencing, is the best method to detect clinically relevant aberrations, because the presence of RNA transcripts ensures that the alterations have been transcribed from DNA to RNA. MI Transcriptome also has the potential to discover previously uncharacterized events, which is important when identifying patients who may derive a strong response to targeted therapy. The test uses the same tissue requirements as Caris’ DNA tumor profiling and delivers results in the same turnaround time.
As the pioneer in precision medicine, Caris was the first to provide comprehensive Whole Exome and Whole Transcriptome sequencing for every patient. Each Caris molecular profiling order includes next-generation sequencing of all 22,000 genes.
Looking for a specific gene? Use the full gene search below to verify that it is included in Caris profiling, or browse the list of genes most commonly associated with cancer.
|Whole Transcriptome Sequencing – Genes most commonly associated with cancer listed below.|
|Fusions (RNA)||Variant Transcripts (RNA)|
|AXL||FGR||ETV4||MET||NTRK1||PIK3CA||RET||THADA||MET Exon 14 Skipping|
NSCLC NCCN guidelines suggest using RNAseq to maximize the number of fusions detected5
|Fusion/Variant||# detected by RNA seq not detected by DNA seq|
N = 232
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