ArcherDX
in Washington DC

The American Association for Cancer Research

AACR Annual Meeting 2017
April 1 - 5 | Booth 2543



archer dollar


Stop by and get your face on a dollar bill!

Stay and learn how Archer® NGS assays can help you to detect relevant mutations in solid tumors, sarcomas and liquid biopsies and also to perform immune repertoire analysis.





archer MET poster

Poster presentation

Comprehensive detection of all major classes of MET deregulation by Anchored Multiplex PCR and next-generation sequencing

Abstract #742
Sunday, April 2, 1:00p-5:00p
Section 31, Poster 8




Brian A. Kudlow1, Josh Haimes1, Marc Bessette1, Namitha Manoj1, Laura M. Griffin1, Danielle Murphy2, Robert Shoemaker2, Jason Amsbaugh1, Joshua Stahl1.
1ArcherDX, Boulder, CO; 2Ignyta, San Diego, CA


Introduction: Deregulation of the proto-oncogene, MET, confers an aggressive phenotype in a variety of human cancers, promoting proliferation, invasive growth and angiogenesis. MET deregulation can be driven by gene amplification, overexpression, exon 14 skipping, gene fusions and single nucleotide variants (SNVs), such as kinase-activating point mutations. MET is a target of intensive drug development efforts, although the various mutated forms of MET exhibit unique drug sensitivities. Therefore, detection of these mutations has an important role in the development of drugs targeting MET, and has the potential to guide treatments for cancers driven by MET deregulation. Next-generation sequencing (NGS) enables comprehensive detection of all mutation types from whole genomes and transcriptomes. However, low detection sensitivity, high input requirement and high costs render these approaches impractical for routine detection of mutations from low-input clinical sample types. We developed a targeted NGS assay based on Anchored Multiplex PCR (AMP™) to detect all types of mutations driving MET deregulation from a single sample.

Methods: AMP only requires a single gene-specific primer for amplification, enabling open-ended capture of DNA and cDNA fragments for NGS-based detection of known and unknown mutations. We developed AMP-based Archer® VariantPlex™ and FusionPlex® library preparation assays to detect mutations from DNA and RNA, respectively. AMP probes were designed to cover the MET gene for detection of copy numbers variants (CNVs) and SNVs from DNA, and known and novel fusions, exon skipping and expression levels from RNA.

Results: We show that the VariantPlex assay enables NGS-based detection of MET amplifications from DNA in concordance with FISH results. Further NGS analysis of RNA from the same sample using the FusionPlex assay revealed the resulting overexpression of MET. We also demonstrate that AMP-enabled open-ended capture of cDNA fragments allows for reliable detection of exon 14 skipping in FFPE samples and in cells, consistent with RT-PCR results. Parallel analysis of DNA from the cell samples revealed splice site mutations that have been previously reported to drive exon 14 skipping. Furthermore, this open-ended capture also permitted identification of a novel GTF2I:MET gene fusion in a patient-derived xenograft model. Finally, we detected an kinase-activating point mutation in MET, p.Y1253D, by analysis of genomic DNA with the VariantPlex NGS assay.

Conclusions: These results show that AMP-based VariantPlex and FusionPlex Assays enable comprehensive detection of multiple mutation types from lowinput clinical sample types, such as FFPE specimens. As MET deregulation can be driven by many different genetic aberrations, this allows for NGS-based characterization of MET deregulation from a single sample.


Archer's newest assays

Reveal ctDNA Kit


Learn more

Mutation profiling from circulating tumor DNA in liquid biopsies

The Archer® Reveal ctDNA™ 28 Kit for Illumina® is an advanced and user-friendly solution for targeted NGS of circulating cell-free tumor DNA e.g., ctDNA, ccfDNA, cfDNA from 28 genes commonly found mutated in solid tumor type cancers.

Immunoverse Kit


Learn more

Immune repertoire sequencing assays

Archer® Immunoverse™ kits are targeted NGS assays to characterize the human immune repertoire from RNA input. Powered by AMP, the lyophilized kits uniquely tag and amplify V(D)J rearrangements for sequencing on Illumina® platforms.

CFTR Kit


Learn more

Comprehensive mutation profiling for cystic fibrosis

The Archer® VariantPlex™ CFTR kit is a targeted NGS assay for comprehensive detection of known and unknown variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.


About ArcherDX


ArcherDX addresses the bottlenecks associated with using NGS by offering a robust platform for targeted sequencing applications.


Archer target enrichment assays utilize AMP chemistry to generate highly enriched sequencing libraries for comprehensive profiling of fusions, CNVs, SNVs and indels. Amplification from independent, unidirectional primers and universal molecular barcoded adapters permit identification of novel gene fusions and mutations with nucleotide-level resolution. Requiring only one intact primer-binding site, AMP chemistry is uniquely suited to amplify small, degraded fragments, enabling solid tumor mutation profiling from FFPE samples and liquid biopsies.


Archer’s easy-to-use, lyophilized kits generate sequencing-ready libraries from RNA, DNA, and liquid biopsy-derived ctDNA. Complemented by the Archer suite of assay design and bioinformatics analysis, Archer’s FusionPlex, VariantPlex and Reveal ctDNA assays facilitate complex mutation identification and discovery, while Immunoverse assays enable quantitative profiling of the expressed immune repertoire.

How to contact us

Address

2477 55th Street, Suite 202

Boulder, CO 80301

Phone

Phone: (877) 771 1093

Phone: (303) 357 9001

All content © 2017 ArcherDX, Inc.

For Research Use Only. Not for use in diagnostic procedures. For Research Use Only. Not for use in diagnostic procedures.