Evaluating gene fusions in solid tumors - clinical experience using an RNA based 53 gene next-generation sequencing panel.

Document Type

Article

Publication Date

4-2019

Keywords

JGM

JAX Source

Cancer Genet 2019 Apr; 233-234:32-42

DOI

https://doi.org/10.1016/j.cancergen.2019.03.001

Abstract

Given the known association of gene fusions with solid tumor morbidity and the need to clarify the role of fusions in therapeutic, prognostic and diagnostic outcomes, we reviewed the positive yield rate for fusions in solid tumors using cases that were referred to our laboratory for clinical testing. We retrospectively evaluated results from 183 solid tumor samples that were received during a 24 month period for testing using the FusionSeq™ assay, an RNA-based Next Generation Sequencing (NGS) panel of 53 genes known to form fusions in solid tumors. Positive yield rate (actionable fusions) was evaluated for all samples tested, as a correlate for clinical utility. Twenty five fusions (actionable, variants of uncertain significance – VUS, and benign) were identified, of which 7 were classified as actionable gene fusions, resulting in an overall positive yield rate of ∼3.8% (7/183). Sixteen mostly novel fusions were classified and reported as VUSs. Five fusion events were classified as false positives, occurring due to mispriming or wild-type read through while 2 were classified as likely benign. Additionally 68% of fusions (17 of 25) detected in our study were present in prostate, colorectal, and gynecological cancers, suggesting that the frequency of fusions identified is dependent on specific tumor type. The high number of novel fusions identified highlights the potential for fusions in precision medicine.

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