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KRAS / NRAS MUTATION ANALYSIS

Test Code: RAS
Description: The KRAS/NRAS mutation assay is designed to accurately identify 30 missense mutations in codons 12,13, 59, 61, 117, and 146 of the KRAS gene and 19 missense mutations in codons 12, 13, and 61 of the NRAS gene using polymerase chain reaction followed by single nucleotide mutation detection using SNaPshot methodology (dideoxy single base extension of oligonucleotide primers). The sensitivity of this assay is approximately 10% KRAS/NRAS mutation detection in a background of KRAS/NRAS wild-type DNA.For a complete list of KRAS/NRAS mutations investigated, see below. 

Tumor-associated KRAS mutations occur most frequently at codons 12, 13, and 61 and lead to constitutive activation of KRAS signaling pathways. Such mutations are found in approximately 40% of colorectal cancers and are associated with lack of response to anti-EGFR antibody therapy. KRAS mutations are also frequently seen in lung adenocarcinomas, ovarian cancers, pancreatic cancer, and carcinomas of the biliary tract, and other malignancies. In those settings, no prognostic or predictive significance has been established to date for KRAS mutations. For the most current information on the clinical significance of KRAS in different types of malignancies, see the following website: http://www.mycancergenome.org/. References: Schubbert et al., Nat Rev Cancer. 2007; Neumann et al., Pathol Res Pract. 2009; Amado et al., J Clin Oncol. 2008.

Tumor-associated NRAS mutations occur most frequently at codons 12, 13, and 61 and lead to constitutive activation of NRAS signaling pathways. Such mutations are found in ∼1-6% of colorectal cancers and are associated with decreased response to anti-EGFR antibody therapy. NRAS mutations are also frequently seen in melanoma, thyroid carcinoma, hepatocellular carcinoma, myeloid leukemias, and non-small cell lung cancer. For the most current information on the clinical significance of NRAS mutations in different types of malignancies, see http://www.mycancergenome.org/. References: Schubbert et al., Nat Rev Cancer, 2007; De Roock et al., Lancet Oncol, 2010; Custodio and Feliu, Crit Rev Oncol Hematol 2013; COSMIC http://cancer.sanger.ac.uk/).

Method
The KRAS/NRAS mutation assay is designed to accurately identify 30 missense mutations in codons 12,13, 59, 61, 117, and 146 of the KRAS gene and 19 missense mutations in codons 12, 13, and 61 of the NRAS gene using polymerase chain reaction followed by single nucleotide mutation detection using SNaPshot methodology (dideoxy single base extension of oligonucleotide primers). The sensitivity of this assay is approximately 10% KRAS/NRAS mutation detection in a background of KRAS/NRAS wild-type DNA. For a complete list of KRAS/NRAS mutations investigated, see the laboratory website stanfordlab.com.

Mutation List:
KRAS Mutations tested:
KRAS Codon 12

p.G12A (c.35G>C)
p.G12D (c.35G>A)
p.G12V (c.35G>T)
p.G12C (c.34G>T)
p.G12R (c.34G>C)
p.G12S (c.34G>A)
p.G12F (c.34_35delinsTT)

KRAS Codon 13
p.G13C (c.37G>T)
p.G13R (c.37G>C)
p.G13S (c.37G>A)
p.G13A (c.38G>C)
p.G13D (c.38G>A)
p.G13V (c.38G>T)

KRAS Codon 59
p.A59T (c.175G>A)
p.A59S (c.175G>T)
p.A59E (c.176C>A)
p.A59G (c.176C>G)

KRAS Codon 61
p.Q61K (c.181C>A)
p.Q61E (c.181C>G)
p.Q61P (c.182A>C)
p.Q61R (c.182A>G)
p.Q61L (c.182A>T)
p.Q61H (c.183A>C)
p.Q61H (c.183A>T)

KRAS Codon 117
p.K117R (c.350A>G)
p.K117N (c.351A>G)
p.K117N (c.351A>T)

KRAS Codon 146
p.A146T (c.436G>A)
p.A146P (c.436G>C)
p.A146V (c.437C>T)

NRAS Mutations tested:

NRAS Codon 12
p.G12S (c.34G>A)
p.G12R (c.34G>C)
p.G12C (c.34G>T)
p.G12D (c.35G>A)
p.G12A (c.35G>C)
p.G12V (c.35G>T)

NRAS Codon 13
p.G13S (c.37G>A)
p.G13R (c.37G>C)
p.G13C (c.37G>T)
p.G13D (c.38G>A)
p.G13A (c.38G>C)
p.G13V (c.38G>T)

NRAS Codon 61
p.Q61K (c.181C>A)
p.Q61E (c.181C>G)
p.Q61P (c.182A>C)
p.Q61R (c.182A>G)
p.Q61L (c.182A>T)
p.Q61H (c.183A>C)
p.Q61H (c.183A>T)


 
 


 
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