Colorectal Cancer

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The KRAS, BRAF, PIK3CA Array

Early Multiplex Detection of Colorectal Cancer from a Single Sample

Individualised treatment based on mutational profiling for metastatic colorectal cancer (mCRC) patients with the discovery of mutant KRAS status and resistance to EGFR antibodies

Detection of BRAF V600E mutation aids targeted drug treatment

Innovative PCR priming technology permits high discrimination between multiple wild type and mutant DNA regions in the KRAS, BRAF or PIK3CA genes

Combination of multiplex PCR and Biochip array hybridisation to enable enhanced specificity

Simultaneously detecting 20 point mutations within the KRAS, BRAF and PIK3CA genes for rapid patient profiling

Suitable for use on the Evidence Investigator, a semi-automated analyser identifying multiple targets in under 3 hours

The Randox KRAS, BRAF, PIK3CA Array is based on a combination of multiplex PCR and biochip array hybridization for high discrimination between multiple wild‑type and mutant DNA regions in the KRAS (mutations in codons 12, 13 and 61), BRAF (V600E mutation) and PIK3CA (mutations in codons 542, 545 and 1,047) genes. Providing there are enough copies of DNA present, ~1% of mutants can readily be detected in a background of wild‑type genomic DNA. A unique primer set is designed for each mutation target (and control), which will hybridize to a complementary discrete test region (DTR) on the biochip array. Each DTR corresponds to a particular mutation target.

Mutations Detectable by KRAS/BRAF/PIK3CA Array

BRAF
Mutation	Base Change	COSMIC ID*
V600E	GTG>GAG	476

KRAS
Mutation	Base Change	COSMIC ID*
G12A	GGT>GCT	522
G12R	GGT>CGT	518
G12D	GGT>GAT	521
G12C	GGT>TGT	516
G12S	GGT>AGT	517
G12V	GGT>GTT	520
G13D	GGC>GAC	532
G13C	GGC>TGC	527
G13R	GGC>CGC	529
Q61K	CAA>AAA	549
Q61L	CAA>CTA	553
Q61R	CAA>CGA	552
Q61H1	CAA>CAC	554
Q61H2	CAA>CAT	555
A146T	GCA>ACA	19404
A146P	GCA>CCA	19905

PIK3CA
Mutation	Base Change	COSMIC ID*
E542K	GAA>AAA	760
E545K	GAG>AAG	763
H1047R	CAT>CGT	775

The Evidence Investigator

Meet the Evidence Investigator

The Randox KRAS, BRAF, PIK3CA array has been developed for the Evidence Investigator, a semi-automated benchtop immunoassay analyser.

This array simultaneously detects 20 mutation points within the KRAS, BRAF and PIK3CA genes. This assay may further aid the selection for CRC patients suitable for EGFR monoclonal antibody therapy. Whilst designed for colorectal cancer, the array has implications for mutation screening in other cancer types.

Want to know more?

Evidence Investigator

Homocysteine is a thio-containing amino acid produced by the intracellular demethylation of methionine. Elevated levels of homocysteine (hyperhomocysteinemia) is more common in women than in men and is associated with a wide array of illnesses. It has also been proven to cause several problems in women including: cardiovascular disease (CVD), colon cancer, pregnancy complications, and birth defects.

Cardiovascular Disease

Elevated levels of circulating homocysteine correlates with an increased risk of vascular occlusion (blockage of a blood vessel). Hyperhomocysteinemia can cause inflammation of the endothelium (thin layer of cells linking the interior blood vessels). Failure to lower homocysteine levels can cause further inflammation of the arteries, veins, and capillaries causing atherosclerosis. Consequently, blood and oxygen supply to tissues is reduced, increasing the risk of cardiovascular disease. Elevated levels correlates with higher diastolic and systolic blood pressure, hypertension. However, this correlation is stronger in women than in men. Women with elevated levels of homocysteine have a 3-fold increased risk of CVD, whereas men have a 2-fold increased risk.

Colon Cancer

Women with hyperhomocysteinemia have an increased risk of colorectal cancer than women with lower levels. Women who present with the highest levels of homocysteine have more than a 70% increased colorectal cancer risk. A correlation between reduced levels of folate and increased levels of homocysteine have been found in women with colorectal adenoma. It is recommended that women with hyperhomocysteinemia and reduced levels of folate should increase their intake of fruit and vegetables to reduce their levels of homocysteine and increase their levels of folate.

Pregnancy Complications and Birth Defects

Homocysteine levels should decline during pregnancy, however, in some cases, levels increase. Hyperhomocysteinemia is associated with foetal neural tube defects which causes various conditions, characterised by placental vasculopathy, including pre-eclampsia, abruption, and recurrent pregnancy loss. It has been identified that folate supplementation can half the risk of foetal neural tube defects. One study found that hyperhomocysteinemia was associated with a 2-fold to 3-fold increased risk for pregnancy-induced hypertension, abrupyio placentae, and intrauterine growth restriction.

Randox Homocysteine Reagent

The Randox Homocysteine assay offers a few unique features:

Limited interference from Bilirubin, Haemoglobin, Triglycerides, and Intralipid, producing more accurate and precise results.
Two-reagent format for convenience and ease of use
Calibrator provided with kit, simplifying the ordering process

Other features include:

Liquid ready-to-use reagents – for optimum user experience
Excellent linearity – 47. 9 μmol/L, ensuring abnormally high levels of homocysteine are detected.
Enzymatic method
Tri-level cardiac control available

If you are a clinician or laboratory who are interested in running assays for women’s health, Randox offer a range of high-quality routine and niche assays including: Adiponectin, Cystatin C, Lipoprotein (a), and Zinc which can be used to diagnose conditions commonly affecting women. These assays can be run on most automated biochemistry analysers.

Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.

For more information, visit: https://www.randox.com/homocysteine or email: reagents@randox.com