RAS Pathway Mutation Profile (KRAS, NRAS), Extended

KRAS and NRAS are guanosine triphosphate (GTP)-binding proteins involved in downstream receptor signaling, which is critical for cell proliferation, survival, and differentiation. Mutations in the KRAS and NRAS oncogene are frequently found in human cancers. They are common in pancreatic, colorectal, lung, bile duct, and thyroid cancer, as well as in melanomas. This assay detects KRAS and NRAS mutations in exons 2, 3, and 4, including codons 12, 13, 59, 61, 117 and 146 and may be used in determination of drug response.

This assay is able to detect 5% mutation in a background of wild-type DNA. This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the US Food and Drug Administration (FDA).

SNaPshot Multiplex PCR (primer extension-based method)

Bae JS, Choi SK, Jeon S, et al. Impact of NRAS mutations on the diagnosis of follicular neoplasm of thyroid. Int J Endocrinol. 2014:289834. PubMed 25254041 Benson AB 3rd, Bekaii-Saab T, Chan E, et al. Rectal cancer. Natl Compr Canc Netw. 2012 Dec 1; 10(12):1528-1564. PubMed 23221790 Benson AB 3rd, Venook AP, Bekaii-Saab T, et al. Colon cancer, version 3.2014. J Natl Compr Canc Netw. 2014 Jul; 12(7):1028-1059. PubMed 24994923 Bokemeyer C, Van Cutsem E, Rougier P, et al. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer. Pooled analysis of the CRYSTAL and OPUS randomized clinical trials. Eur J Cancer. 2012 Jul; 48(10):1466-1475. PubMed 22446022 Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME study. J Clin Oncol.2010 Nov 1; 28(31):4697-4705. PubMed 20921465 Thumar J, Shahbazian D, Aziz SA, Jilaveanu LB, Kluger HM. MEK targeting in N-RAS mutated metastatic melanoma. Mol Cancer. 2014 Mar 4; 13:45-54. PubMed 24588908