K-RAS Mutation Testing

Mutations in the K-RAS oncogene are frequently found in human cancers. They are common in colorectal cancer, pancreatic cancer and others. These mutations can help indicate prognosis and may be predictive of drug response.

Lab21 offers the CE-Marked K-RAS assay developed by DxS Genotyping, a highly selective and robust test (combining Scorpions and ARMS® (allele specific PCR) technologies), which detects the 7 key mutations in the K-RAS gene.

Recent clinical data has established that 40% of colorectal tumours may carry a mutated K-RAS gene and these tumours show little or no response to some therapies, including Panitumumab (Amgen) and Cetuximab (Erbitux, Merck). By prescreening for the presence of these mutations this provides clinicians with an opportunity to target the drugs to a subset of patients more likely to respond well.

References

• E. Massarelli, M. Varella-Garcia, X. Tang, A. C. Xavier et al. (2007). KRAS Mutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer. Clin Cancer Res 2007; 13 (10).
• William Pao, Theresa Y. Wang, Gregory J. Riely, Vincent A. Miller, Qiulu Pan, Marc Ladanyi et al. (2005). KRAS mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib.  PloS Medicine 2(1): 57-61.
• D. A. Eberhard, B. E. Johnson, L.C. Amler, A. D. Goddard et al (2005). Mutations in the EGFR and in K-RAS are predictive and prognostic indicators in patients with NSCLC treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 23: 5900-5909.
• L. Toschi & F. Cappuzzo. (2007) Understanding the new genetics of responsiveness to EGFR tyrosine kinase inhibitors. Oncologist 12; 211-220.
• Sae-Won Han, Tae-You Kim, Yoon Kyung Jeon, Pil Gyu Hwang et al. (2006). Optimization of Patient Selection for Gefitinib in Non-Small Cell Lung Cancer by combined analysis of Epidermal Growth Factor Receptor Mutation, K-RAS Mutation, and AKT Phosphorylation.  Clin Cancer Res 12(8):2538-2544.
• Newton CR, Graham A, Heptinstall LE, Powell SJ, Summers C et al. (1989). Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS) Nucleic Acids Res. 17 (7): 2503-16
• Lievre A, Bachet J-B et al. (2008) KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 26: 374-379.