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The Pathologist / App Notes / 2017 / Evaluating Expanded RAS Mutations in Colorectal Adenocarcinoma Using a Targeted, High Throughput, Cost-Effective Solution

Evaluating Expanded RAS Mutations in Colorectal Adenocarcinoma Using a Targeted, High Throughput, Cost-Effective Solution

11/27/2017

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Bobbie Sutton, PhD, The Medical Foundation, South Bend, IN; Darryl Irwin, PhD, Agena Bioscience, and Divya Neelam*, Agena Bioscience
*Corresponding author: Divya.Neelam@AgenaBio.com

Introduction

It has been known for several years that patients with metastatic colorectal adenocarcinoma (mCRC) who harbor an activating mutation in the Kirsten rat sarcoma viral oncogene homolog (KRAS) exon 2 will not benefit from monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR). Recent research evaluating anti-EGFR monoclonal antibodies has indicated that up to 20% of the KRAS exon 2 wild type tumors may contain other RAS mutations that are similarly predictive of drug resistance.1,2 Currently, common KRAS testing methodologies only assay codons 12/13 in exon 2 and sometimes codon 61 in exon 3. This application note describes the development of the Assays by Agena (AbA) OncoFOCUS Panel v3 for the retrospective testing of archived CRC samples. The panel, for use on the MassARRAY® System, was developed to include expanded coverage of KRAS and NRAS mutations.

Assay Design
Agena Bioscience’s OncoFOCUS Panel v1 is a set of pre-validated assays covering 200+ somatic mutations in four key oncogenes observed in lung, colorectal, and metastatic melanoma tumors. The panel was designed to detect significant driver mutations in EGFR, KRAS, NRAS, and BRAF with extensive coverage of EGFR exon 19 and 20 insertions and deletions. The AbA OncoFOCUS+KIT Panel v2 was developed to include mutations in the c-KIT oncogene for additional coverage of melanomas.


>> Download the full Application Note as PDF

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