title: RAS testing in metastatic colorectal cancer: advances in Europe.
abstract: Personalized medicine shows promise for maximizing efficacy and minimizing toxicity of anti-cancer treatment. KRAS exon 2 mutations are predictive of resistance to epidermal growth factor receptor-directed monoclonal antibodies in patients with metastatic colorectal cancer. Recent studies have shown that broader RAS testing (KRAS and NRAS) is needed to select patients for treatment. While Sanger sequencing is still used, approaches based on various methodologies are available. Few CE-approved kits, however, detect the full spectrum of RAS mutations. More recently, "next-generation" sequencing has been developed for research use, including parallel semiconductor sequencing and reversible termination. These techniques have high technical sensitivities for detecting mutations, although the ideal threshold is currently unknown. Finally, liquid biopsy has the potential to become an additional tool to assess tumor-derived DNA. For accurate and timely RAS testing, appropriate sampling and prompt delivery of material is critical. Processes to ensure efficient turnaround from sample request to RAS evaluation must be implemented so that patients receive the most appropriate treatment. Given the variety of methodologies, external quality assurance programs are important to ensure a high standard of RAS testing. Here, we review technical and practical aspects of RAS testing for pathologists working with metastatic colorectal cancer tumor samples. The extension of markers from KRAS to RAS testing is the new paradigm for biomarker testing in colorectal cancer.
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, Netherlands. Han.vanKrieken@radboudumc.nl.
authors.forename: J Han J M
authors.initials: JH
authors.lastname: Van Krieken
authors.affiliation: Curie Institute, Paris, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Rouleau
authors.affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, Netherlands.
authors.forename: Marjolijn J L
authors.initials: MJ
authors.lastname: Ligtenberg
authors.affiliation: Cell Biology and Biotherapy Unit, INT-Fondazione Pascale, Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Normanno
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.|Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Patterson
authors.affiliation: Institute of Pathology, University of Munich, Munich, Germany.|German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D005060:Europe; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D018579:Patient Selection; D057285:Precision Medicine / Q000379:methods*; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D018631:ras Proteins
keywords: Biomarkers; Colorectal cancer; Quality assurance programs; RAS; Sequencing