Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 3

5603 - Development of a comprehensive next-generation targeted sequencing assay for detection of gene-fusions in solid tumors

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Translational Research

Tumour Site

Presenters

Vinay Mittal

Citation

Annals of Oncology (2019) 30 (suppl_5): v760-v796. 10.1093/annonc/mdz268

Authors

V.K. Mittal1, S.P. Myrand1, D. Cyanam2, P.D. Williams1, G.G. Bee3, A. Marcovitz4, R. Gottimukkala4, F. Hyland5, C. Allen6, E. Wong-Ho4, S. Sadis1, C. Van Loy3, J. Kilzer3, N. Khazanov1

Author affiliations

  • 1 Clinical Sequencing Division, Thermo Fisher Scientific, 48104 - Ann Arbor/US
  • 2 Clinical Sequencing, Thermo Fisher Scientific, 48104 - Ann Arbor/US
  • 3 Clinical Sequencing Division, Thermo Fisher Scientific, 92008 - Carlsbad/US
  • 4 Clinical Sequencing Division, Thermo Fisher Scientific, 94080 - South San Francisco/US
  • 5 Csd, Thermo Fisher Scientific, 94080 - San Francisco/US
  • 6 Field Applications, Thermo Fisher Scientific, PA49RF - Paisley/GB

Resources

Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

Abstract 5603

Background

Gene fusions caused by chromosomal rearrangements play an important role in oncogenesis, the progression of cancer and the selection of targeted therapies. Next-generation sequencing (NGS) using RNA enables sensitive, specific and precise detection of potentially clinically relevant gene fusions, especially when the fusion breakpoint is known. We have developed an NGS solution appropriate for FFPE tissues to detect fusion biomarkers in routine clinical research.

Methods

Fusion content was selected based on prioritization of actionability, verified fusion isoforms reported in the literature and collaborations, as well as prevalence of solid tumor fusion driver genes. The assay was designed to use Ion AmpliSeq multiplex PCR chemistry using manual or automated library preparation, automated templating on the Ion Chef, and sequencing on the Ion Torrent GeneStudioTM S5 sequencing platform. The analysis was supported by fully automated analysis software that performs sample QC, read-filtering, fusion calling and reporting. Streamlined access to decision support software was enabled by Oncomine™ Reporter.

Results

Over 1200 targeted isoforms from over 50 known fusion driver genes were incorporated into the assay that included prominent fusion drivers such as ALK, RET, ROS1, NTRK1/2/3 and FGFR1/2/3, and intragenic fusion events in MET, EGFR, BRAF and AR. The assay also reported non-targeted fusion events in relevant driver genes by using a novel statistically significant expression imbalance algorithm comparing 5’- and 3’- end gene expression. A preliminary development study was performed using commercially available total RNA for a Tri-Fusion control and Seraseq™ Fusion RNA Mix v3 where all of the expected fusions were detected with 100% sensitivity and specificity. Results were also concordant when characterized FFPE tumor samples with known fusion targets were tested using the assay.

Conclusions

A comprehensive NGS assay was developed to support clinical research in oncology for detecting relevant RNA structural alterations from solid tumor FFPEs. An update on assay performance will be presented.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Thermo Fisher Scientific.

Funding

Has not received any funding.

Disclosure

V.K. Mittal: Shareholder / Stockholder / Stock options, Full / Part-time employment: Thermo Fisher Scientific. S.P. Myrand: Shareholder / Stockholder / Stock options, Full / Part-time employment: Thermo Fisher Scientific. D. Cyanam: Shareholder / Stockholder / Stock options, Full / Part-time employment: Thermo Fisher Scientific. P.D. Williams: Shareholder / Stockholder / Stock options, Full / Part-time employment: Thermo Fisher Scientific. G.G. Bee: Shareholder / Stockholder / Stock options, Full / Part-time employment: Thermo Fisher Scientific. A. Marcovitz: Shareholder / Stockholder / Stock options, Full / Part-time employment: Thermo Fisher Scientific. R. Gottimukkala: Shareholder / Stockholder / Stock options, Full / Part-time employment: Thermo Fisher Scientific. F. Hyland: Shareholder / Stockholder / Stock options, Full / Part-time employment: Thermo Fisher Scientific. C. Allen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Thermo Fisher Scientific. E. Wong-Ho: Shareholder / Stockholder / Stock options, Full / Part-time employment: Thermo Fisher Scientific. S. Sadis: Shareholder / Stockholder / Stock options, Full / Part-time employment: Thermo Fisher Scientific. C. Van Loy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Thermo Fisher Scientific. J. Kilzer: Shareholder / Stockholder / Stock options, Full / Part-time employment: Thermo Fisher Scientific. N. Khazanov: Shareholder / Stockholder / Stock options, Full / Part-time employment: Thermo Fisher Scientific.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.