1164P - Comprehensive profiling of thyroid and lung cancers by anchored multiplex PCR and next-generation sequencing

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Presenter Joshua Stahl
Citation Annals of Oncology (2016) 27 (6): 401-406. 10.1093/annonc/mdw380
Authors J. Stahl, J.D. Haimes, L. Johnson, J. Covino, N. Manoj, M. Bessette, E. Baravik, A. Licon, R.D. Walters, L. Griffin, J.W. Myers, B. Culver, B. Kudlow
  • Research And Development, ArcherDX, Inc., 80301 - Boulder/US

Abstract

Background

Thyroid and lung cancer tumorigenesis can be driven by many mutation types occurring across a large set of genes. These include single nucleotide variants (SNVs), insertions and deletions (indels), copy number variants (CNVs) and fusions. As such, a comprehensive assay for multiple classes of genomic aberrations targeting a spectrum of relevant genes has significant implications for the characterization of thyroid and lung tumors. Anchored Multiplex PCR (AMP™) is a target enrichment strategy engineered to preserve the complexity of degraded samples by ligating molecular barcodes with a universal primer binding site for amplification. This enables next generation sequencing (NGS)-based detection of known and novel fusions from RNA, as well as RNA-based variant detection and expression analysis. In addition, high complexity DNA-based libraries allow for high-confidence SNV/indel and CNV detection.

Methods

Sixty two non-small cell lung carcinoma samples were subjected to AMP-based NGS using Archer™ VariantPlex™ and FusionPlex™ CTL parallel assays. Analysis of all samples was carried out with Archer Analysis.

Results

Our data show that parallel interrogation of DNA and RNA using VariantPlex and FusionPlex CTL assays, respectively, enables simultaneous detection of SNVs, indels, CNVs and fusions from low-input clinical sample types. Furthermore, we show that characterization of gene expression, including detection of splice variants, expression imbalances and whole gene expression levels provides orthogonal verification of detected mutations.

Conclusions

These results demonstrate that AMP-based libraries support simultaneous NGS-based detection of multiples types of genomic aberrations across many genes in lung and thyroid cancer. Furthermore, combined use of RNA- and DNA-based libraries offer cross-validation of findings within a sample.

Clinical trial identification

Legal entity responsible for the study

ArcherDX, Inc.

Funding

ArcherDX, Inc.

Disclosure

J. Stahl, J.D. Haimes, L. Johnson, J. Covino, N. Manoj, M. Bessette, E. Baravik, A. Licon, R.D. Walters, L. Griffin, B. Culver, B. Kudlow: Full-time employee at ArcherDX, Inc.