Molecular Diagnostics

Warnex Medical Laboratories uses molecular biology techniques to investigate disease states in order to assist healthcare professionals in preventing, diagnosing, monitoring and treating disease. Warnex offers a number of DNA-oriented genetic predisposition and tracking tests in various fields of medicine.

Oncology

Chronic Myeloid Leukemia - bcr-abl

Chronic myeloid leukemia (CML) is a cancer of blood cells, characterized by replacement of the bone marrow with malignant, leukemic cells. Many of these leukemic cells can be found circulating in the blood and can cause enlargement of the spleen, liver, and other organs. The early diagnosis of CML is extremely important since it is a disease, which if detected early enough in its course, can be cured. CML is usually diagnosed by finding a specific chromosomal abnormality called the "bcr-abl rearrangement" or "Philadelphia chromosome".

Warnex's diagnostic tests are performed using polymerase chain reaction (PCR) technology. This highly sensitive and reliable technology makes it possible to detect one rearranged cell among a million cells. This is far superior to the accuracy of traditional cytogenetics or of the FISH method (fluorescent in situ hybridization).

Warnex offers 3 different tests to detect and to monitor the CML disease: 1) a qualitative test to detect the presence of the bcr-abl rearrangement; 2) a quantitative real-time PCR test to monitor the levels of bcr-abl rearrangement during the course of a patient's treatment; and 3) a mutation analysis of the bcr-abl gene for patients not responding to treatment.

Acute Myeloid Leukemia - NPM1

Acute myeloid leukemia (AML) is an aggressive form of cancer that begins in cells that normally develop into blood cells. The disease causes the rapid proliferation of abnormal cells, which accumulate in the bone marrow and interfere with the production of normal blood cells. A recent discovery showed that many AML patients have mutations in the NPM1 gene. Testing for the presence or absence of the NPM1 mutation contributes to improving the diagnosis, prognosis and monitoring of the disease. This test can therefore help physicians select patients with a good prognosis of benefiting from intensive chemotherapy, while sparing others with a low probability of benefit from the toxic treatment. The NPM1 test may also be used to monitor AML patients for residual disease during chemotherapy. Stratification of AML patients is also necessary for anti-AML drug clinical trials. Warnex offers a screening test using PCR for the NPM1 mutation for the diagnosis, stratification and monitoring of patients with AML.

Myeloproliferative Disorders - JAK2

Myeloproliferative disorders are a group of diseases including polycythemia vera (Vaquez' disease), essential thrombocythemia (ET) and idiopathic myelofibrosis. These diseases are linked to an anomaly of the regulation of production of blood cells due to an overgrowth of the precursor cells in the bone marrow. One of the complications of myeloproliferative disorders is a tendency for thrombosis. The detection of the V617F mutation of the JAK2 gene can help to distinguish between myeloproliferative disorders and reactive conditions such as secondary thrombocytosis and erythrocytosis. Warnex offers a screening test using PCR for the V617F mutation of the JAK2 gene.

Colorectal Cancer - K-ras

Colorectal cancer, also called colon cancer or large bowel cancer, includes cancerous growths in the colon, rectum and appendix. Many colorectal cancers are thought to arise from polyps in the colon. These growths are usually benign, but some may develop into cancer over time. Current treatment strategies for colorectal cancer include therapy targeting the epidermal growth factor receptor (EGFR). However, studies have shown that a mutation in the K-ras gene gives rise to resistance to anti-EGFR therapy. The incidence of K-ras mutations is about 40% in colorectal cancer tumours. The American Society for Clinical Oncology (ASCO) recently released an opinion recommending routine K-ras gene testing to guide treatment for metastatic colorectal cancer. Warnex’s mutation analysis of the K-ras gene provides valuable information to evaluate a patient’s response to EGFR targeting compounds.

Metastatic Cancer and Cancer of Unknown Primary (CUP) - miRview^TM mets

The miRview^TM mets test can accurately identify the primary tumor site in patients presenting a metastatic cancer, as well as in patients whose tumor has not been identified, and consequently been labeled Cancer of Unknown Primary (CUP). As metastases need to be treated according to their primary origin, accurate identification of the metastases' primary origin can be critical for determining appropriate treatment. Current diagnostic methods to identify the origin of a metastasis include a wide range of costly, time consuming, and at times inefficient tests. miRview^TM mets offers physicians a fast, accurate, and easy to interpret diagnosis of the predicted primary origin. For more information, visit www.mirviewdx.com.

Non-Small Cell Lung Cancer (NSCLC) - miRview^TM squamous

Using a single microRNA, miRview^TM squamous differentiates squamous from non-squamous non-small cell lung cancer (NSCLC) patients. When administered a targeted therapy, whether currently available or under development, patients with squamous cell carcinoma of the lung have demonstrated varying response patterns ranging from a high incidence of severe or fatal internal bleeding in the lungs to overall poor response to treatment. Current methods for differentiating squamous from non-squamous non-small cell lung cancer are not standardized, are difficult to reproduce, and have low accuracy. miRview squamous produces a single score which indicates whether a sample is squamous or non squamous NSCLC. For more information, visit www.mirviewdx.com.

Mesothelioma - miRview^TM meso

The miRview^TM meso test leverages microRNA's high specificity as biomarkers to differentiate mesothelioma, a cancer connected to asbestos exposure, from other carcinomas in the lung. As mesothelioma patients require specific treatment regimens, accurately diagnosing mesothelioma is critical. Currently, there is no single diagnostic test that is entirely conclusive for this differentiation. In addition, pathological diagnosis may suffer from significant inter-observer variability, and in the absence of a single specific and reliable marker, mesothelioma can be difficult to identify from other cancers. miRview^TM meso is highly accurate test which may also assist physicians to rule out mesothelioma in patients diagnosed with adenocarcinoma in the lung who have been exposed to mesothelioma-related substances, primarily asbestos particles and heavy metals. For more information, visit www.mirviewdx.com.

Haematology/Coagulation

Factor V Leiden Thrombophilia

The Factor V Leiden mutation results in thrombophilia, an increased tendency to form abnormal blood clots in blood vessels. This mutation has been observed in patients with idiopathic thrombotic manifestations and has also been identified in a significant number of women who have had obstetrical complications (preeclampsia, placental detachment, stillborn baby, intra-uterine growth retardation, repeated pregnancy losses). For young women with the factor V Leiden mutation, taking birth control pills increases the risk of thrombosis. Warnex offers a screening test using PCR for the V506 Leiden mutation.

Prothrombin Mutation

A prothrombin mutation, also known as factor II mutation, causes the body to produce too much of the prothrombin protein, which makes blood more likely to clot. The prevalence of the prothrombin mutation is high among patients who have presented with cerebral thrombosis (arterial or venous) or with pulmonary embolism. Patients with the factor II mutation 20210A have a greater risk of suffering a myocardial infarction. Smoking, as well as metabolic risk factors such as diabetes, hypertension and hypercholesterolemia, increase the risk of myocardial infarction in these patients. Warnex offers a screening test using PCR for the 20210A mutation of the factor II gene.

Homocysteine Metabolism

A genetic mutation in methylenetetrahydrofolate reductase (MTHFR), an enzyme required for efficient homocysteine metabolism, has been associated with early arteriosclerotic vascular diseases and venous thrombosis. This mutation manifests a high serum level of homocysteine, which is a risk factor for cardiovascular, cerebrovascular and peripheral vascular diseases. Warnex offers a screening test using PCR for the C677T mutation of the MTHFR gene. However, screening for this mutation does not replace homocysteine testing since there can be other etiologies to its increased level.

Hemochromatosis

Hemochromatosis is a disorder that increases the amount of iron that the body absorbs from the gut. Symptoms are caused by this excess iron being deposited in multiple organs of the body. Most commonly, excess iron in the liver causes cirrhosis, which may develop into liver cancer. Iron deposits in the pancreas can result in diabetes. Similarly, excess iron stores can cause cardiomyopathy, pigmentation of the skin, and arthritis. Most cases of hemochromatosis are caused by mutations in the HFE gene. The discovery of this gene has allowed the early diagnosis of this disease, with the possibility of detecting the mutation before any significant intra-tissue accumulation of iron becomes apparent. Warnex offers screening tests using PCR for the C282Y and H63D mutations of the HFE gene.