Abstract 4238
Background
We developed a tumor-only NGS assay (TruSight assay), a 523 gene panel covering 1.94 megabases (Mb), that detects small DNA variants, provides a microsatellite instability (MSI) score, and estimates tumor mutational burden (TMB) from FFPE tissue DNA. We demonstrate the assay’s ability to detect a variety of biomarkers compared to various orthogonal methods across a range of solid tumor tissues. We also demonstrate accuracy in determining TMB status, using a clinically based cutoff, in non-small cell lung cancer (NSCLC) FFPE samples compared to tumor-normal whole exome sequencing (WES).
Methods
The study used ∼400 paired tumor-normal FFPE samples from 7 tumor types, including 240 NSCLC. Tumor samples were tested using the verified assay workflow including software analysis. All tumor and normal FFPE were tested with internal WES (with an independent analysis pipeline) and most with a commercial MSI PCR kit (Promega). The TMB score threshold, in mutations (mut)/Mb, was established for the TruSight assay and WES using 119 independent NSCLC FFPE samples and correlated with an external published cutoff.
Results
Across different tumor types, there was high concordance in small DNA variant calling (>95% positive percent agreement [PPA], >99% negative percent agreement [NPA]) between the TruSight assay and WES. For MSI, >95% PPA and 100% NPA were achieved between the TruSight assay and MSI-PCR. TMB scores from the TruSight assay showed good correlation with WES TMB scores (R2 >0.95 on linear regression). Among the NSCLC samples, TMB scores (range 0 – 184.6 mut/Mb) determined by the TruSight assay correlated well with WES (R2 0.94). Using cutoffs of 12.3 and 8.3 mut/Mb (TruSight assay and WES, respectively) to assign TMB High and Low statuses, overall percent agreement (OPA) was 85%.
Conclusions
The tumor-only TruSight assay showed high accuracy in detecting biomarkers across a range of solid tumors. The assay showed a good correlation in TMB score and agreement in TMB status with tumor-normal WES in a collection of NSCLC samples.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Illumina.
Disclosure
I. Deras: Shareholder / Stockholder / Stock options, Full / Part-time employment: Illumina; Shareholder / Stockholder / Stock options: Bristol-Myers Squibb. T. Du: Shareholder / Stockholder / Stock options, Full / Part-time employment: Illumina. C. Zhao: Shareholder / Stockholder / Stock options, Full / Part-time employment: Illumina. N. Haseley: Full / Part-time employment: Illumina. A. Yazdanparast: Full / Part-time employment: Illumina. T. Jiang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Illumina; Shareholder / Stockholder / Stock options: Bristol-Myers Squibb. A. Mentzer: Shareholder / Stockholder / Stock options, Full / Part-time employment: Illumina. A. Purdy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Illumina; Shareholder / Stockholder / Stock options: Bristol-Myers Squibb. B. Crain: Shareholder / Stockholder / Stock options, Full / Part-time employment: Illumina. C. Echegaray: Shareholder / Stockholder / Stock options, Full / Part-time employment: Illumina. D. Lee: Full / Part-time employment: Illumina. J. Lee: Full / Part-time employment: Illumina. J. Silhavy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Illumina. K. O’Brien: Shareholder / Stockholder / Stock options, Full / Part-time employment: Illumina. R. Vijayaraghavan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Illumina. R. Garcia: Full / Part-time employment: Illumina. R. Haigis: Shareholder / Stockholder / Stock options, Full / Part-time employment: Illumina. T. Pawlowski: Shareholder / Stockholder / Stock options, Full / Part-time employment: Illumina. J. Dockter: Shareholder / Stockholder / Stock options, Full / Part-time employment: Illumina.
Resources from the same session
4868 - Evaluation of markers associated with efficacy of abiraterone acetate plus prednisone (AAP) in patients (pts) with castration-sensitive prostate cancer (mCSPC) from the LATITUDE study
Presenter: Kim Chi
Session: Poster Display session 3
Resources:
Abstract
4837 - LRP2, a potential new biomarker for Chinese younger aged intrahepatic cholangiocarcinoma patients
Presenter: Xiaoliang Shi
Session: Poster Display session 3
Resources:
Abstract
1286 - Reanalysis of the efficacy of molecular targeted agents (MTAs) given in the randomized trial SHIVA01 according to the ESMO ESCAT scale of actionability
Presenter: Aurelie Moreira
Session: Poster Display session 3
Resources:
Abstract
2736 - Comparison of Platforms for Determining Tumor Mutational Burden (TMB) From Blood Samples in Patients With Non-Small Cell Lung Cancer (NSCLC)
Presenter: Jonathan Baden
Session: Poster Display session 3
Resources:
Abstract
5045 - Comprehensive Pan-Cancer analysis of somatic mutations in drug transporters to reveal acquired and intrinsic drug resistance in 3149 metastatic cancer patients
Presenter: Sander Bins
Session: Poster Display session 3
Resources:
Abstract
4577 - Pan-Cancer Genomic Landscape of the Cyclin D1/FGF3,4,19 (11q13) Amplicon Including Associations with HPV Status, and ESR1 and AR Alterations
Presenter: Jennifer Johnson
Session: Poster Display session 3
Resources:
Abstract
5366 - Co-occurrence of NTRK fusions with other genomic biomarkers in cancer patients
Presenter: Xiaolong Jiao
Session: Poster Display session 3
Resources:
Abstract
4084 - Prospective comparative study of next-generation sequencing on fine needle aspirations versus core needle biopsies in cancer patients included in SHIVA02 trial
Presenter: Julien Masliah-Planchon
Session: Poster Display session 3
Resources:
Abstract
6017 - First national External Quality Assessement for the interpretation of somatic variants: assessment of 25 variants in colorectal, lung, ovarian cancers and melanoma in France
Presenter: Etienne Rouleau
Session: Poster Display session 3
Resources:
Abstract
2283 - Prospective testing of circulating tumor DNA in metastatic breast cancer facilitates clinical trial enrollment and precision oncology
Presenter: Andjelija Bujak
Session: Poster Display session 3
Resources:
Abstract