K-RAS Exon 2 sequencing K-RAS. Condon 12, 13 and 61 pathological variations found in Colorectal Cancer - Test # 1333

Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region.The RAS proteins are GDP/GTP-binding proteins that act as intracellular signal transducers. The cellular homologues of the viral Harvey and Kirsten transforming ras sequences were first identified in the rat genome in 1981 (1) and were subsequently found in the mouse2 and human3 genomes. These discoveries revealed that the ras oncogenes behaved, at least superficially, like the src oncogene of Rous sarcoma virus (RSV), the origins of which were first reported in 1976 (2). Thus, protooncogenes residing in the genomes of normal cells can be activated into potent oncogenes by retroviruses, which acquire these sequences and convert them into active oncogenes. The Harvey sarcoma virus-associated oncogene was named Ha-ras (H-ras in mammals), whereas that of Kirsten sarcoma virus was termed Ki-ras (K-ras in mammals). Mutant alleles of these ras sequences were soon discovered in many human cancer cell lines, including those of the bladder, colon and lungs(3). The most pathological variations in different codons and its prevalence in cancer cells are in table 1.

Table 1 KRAS Mutation Frequency
Mutation Name Codon Position Frequency
c.34G>T (G12C) Codon 12 7.9%
c.34G>C (G12R) Codon 12 1.2–1.4%
c.34G>A (G12S) Codon 12 4.9–5.7%
c.35G>C (G12A) Codon 12 6.2–6.6%
c.35G>A (G12D) Codon 12 33.5–34.4%
c.35G>T (G12V) Codon 12 21.9–24.4%
c.37G>T (G13C) Codon 13 < 1%
c.37G>C (G13R) Codon 13 < 1%
c.37G>A (G13S) Codon 13 <1%
c.38G>C (G13A) Codon 13 <1%
c.38G>A (G13D) Codon 13 18.9–19.2%
c.38G>T (G13V) Codon 13 <1%
c.64C>A (Q22K) Codon 22 < 1%
c.181C>A (Q61K) Codon 61 < 1%
c.182A>T (Q61L) Codon 61 < 1%
c.182A>C (Q61P) Codon 61 < 1%
c.182A>G (Q61R) Codon 61 < 1%
c.183A>C (Q61H) Codon 61 < 1%
c.183A>T (Q61H) Codon 61 < 1%
c.351A>C (K117N) Codon 117 < 1%
c.351A>T (K117N) Codon 117 < 1%
c.436G>C (A146P) Codon 146 < 1%
c.436G>A (A146T) Codon 146 0.6–1.2%
c.437C>T (A146V) Codon 146 < 1%

Normal Sample Report

Indications of Test

Clinical Use

Determine mutations in the Exon 2 K-RAS gene.

Determine eligibility for therapies targeting epidermal growth factor receptor (EGFR)

Molecular test for colorectal cancer screening of fluid or human tissue using molecular genetic techniques (e.g., Cologuard, ColoSure, PreGen-Plus) experimental and investigational.

NON-INVASIVE NASAL TEST TO IMPROVE LUNG CANCER DIAGNOSIS using nasal and bronchial epithelium by a swab. Contact us.

Clinical Background

Mutations in the RAS gene family (HRAS, KRAS, and NRAS) have been observed in a variety of cancers. They are activating mutations that result in continual signal transduction, stimulating downstream signaling pathways involved in cell growth, proliferation, invasion, and metastasis.

This test detects specific mutations in the KRAS gene in the DNA of cancer cells and tissue. The presence of these mutations may indicate that certain drugs will not be effective in treating the cancer.

KRAS is a short name for the gene v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog. It is one of a group of genes involved in a pathway called the epidermal growth factor receptor (EGFR) pathway. This complex signaling pathway involves numerous components that relay signals from outside of the cell to within the cell to help regulate cell growth, division, survival and death.

In many normal cells, binding of epidermal growth factor (EGF) to its receptor (EGFR) on the surface of the cell is an important signal to cell growth and division. Other signals in the pathway involve a class of proteins called tyrosine kinase (TK) enzymes and a protein produced by the KRAS gene. Normally, the components of the pathway interact in the regulation of cell growth and division and do not individually stimulate cell proliferation.

However, in some cancers, EGFR becomes active even in the absence of EGF, leading to uncontrolled cell growth and division. Drugs that inhibit EGFR or tyrosine kinase enzymes are often helpful for treating such cancers. Some of these cancers, though, have a mutation in the KRAS gene that produces an abnormal K-Ras protein. The abnormal protein is always active and can stimulate cell growth even in the absence of signals from EGFR and TK. In such cancers, drugs that inhibit EGFR or TK will not be effective.

KRAS mutations are found in many different types of cancers but have been most extensively studied in colon cancer and non-small cell lung cancer. Approximately 40% of colon cancers and 20% of lung cancers will have KRAS mutations.

Specimen Requirements

Requisition form. Test number 1333

Specimen and Volume: Whole blood- Collect 0.3-5 cc of blood in EDTA or ACD BD Vacutainer tubes guide. Embedded Tissue. Other types of tissue may be accepted (please call 818-789-1033 to verify before sending). Dry blood spot DBS, feces (please call 818-789-1033 to verify before sending), or corporal fluid.

Contact your doctor's office or FirmaLab for buccal swab kits. Buccal Swab Kit Instructions

Temperature: Specimen can be at room temperature and needs to be at the laboratory no more than 72hrs after collection. Do not freeze whole blood .

Turn around time: 5-7 days

Policy: General rejection criteria for specimens received at the laboratory may be developed. Additionally, each test may have specific requirements and shall have specific rejection criteria under the Specimen Requirements of the NCCLS formatted description of the test.

Procedure: Below are general rejection criteria. If the specimen must be rejected based on the following criteria, or specific criteria for the requested test:

  1. The test requisition form has missing information. Requisition must contain the required information including:
    • Requesting party and referring authority, usually a healthcare professional.
    • Patient identifying information - Name or alias if anonymous;
    • Test requested, Clinical indication for testing;
    • Date and time of specimen collection;
    • Type of sample (e.g. whole blood or epithelial cells obtained by buccal swab);
    • All other identifying information (e.g. social security number, telephone number, hospital ID, sex … etc.) is optional, but useful for accurate differentiating between patients with similar names.
  2. Label is unclear;
  3. Blood specimen is from a recipient of bone marrow transplant;
  4. Specimen is inappropriate for test requested;
  5. Blood sample is clotted or hemolyzed;
  6. Incorrect container or Vacutainer used;


1.Ahrendt, S. A., Decker, P. A., Alawi, E. A., Zhu, Y., Sanchez-Cespedes, M., Yang, S. C., Haasler, G. B., Kajdacsy-Balla, A., Demeure, M. J., Sidransky, D. Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung. Cancer 92: 1525-1530, 2001. [PubMed: 11745231, related citations] [Full Text]

2.Aoki, Y., Niihori, T., Kawame, H., Kurosawa, K., Ohashi, H., Tanaka, Y., Filocamo, M., Kato, K., Suzuki, Y., Kure, S., Matsubara, Y. Germline mutations in HRAS proto-oncogene cause Costello syndrome. Nature Genet. 37: 1038-1040, 2005. [PubMed: 16170316, related citations] [Full Text]

3.Barbie, D. A., Tamayo, P., Boehm, J. S., Kim, S. Y., Moody, S. E., Dunn, I. F., Schinzel, A. C., Sandy, P., Meylan, E., Scholl, C., Frohling, S., Chan, E. M., and 23 others. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 462: 108-112, 2009. [PubMed: 19847166, related citations] [Full Text]


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