Welcome

Please select your view

banner-8-1800x424jpg

Haematology & Oncology

Haematology

Factor V Leiden

The Factor V Leiden mutation is present in 45% of familial thrombophilia and is the most common genetic risk factor identified in patients with thrombosis. Heterozygous individuals have an approximate 8-fold increase risk for venous thrombosis. The relative increase in risk for homozygous individuals is approximately 80-fold. When the mutation is found, family studies are recommended. Also, full thrombophilic screens are suggested, if not previously performed

Prothrombin 20,210

The Prothrombin 20,210 gene mutation is the second most common cause of inherited thrombophilia. Carriers have a predisposition to elevated prothrombin concentrations. Heterozygotes for the mutation constitute approximately 2 % of the normal population and up to 20% of those with recurrent or familial thrombotic events. Heterozygotes carry an estimated 2-5 fold increased risk of venous thrombosis. Thrombosis risk increases synergistically in the presence of the Factor V Leiden mutation. When the mutation is found, family studies are recommended. Also, full thrombophilic screens are suggested, if not previously performed.

MTHFR

High blood levels of an amino acid called homocysteine, is recognized as a risk factor for coronary artery disease, venous thrombosis and stroke. High blood levels have also been associated with neural tube defects, stillbirths and recurrent pregnancy loss. The major cause of high homocysteine levels (or hyperhomocysteinemia) is folate deficiency. Other factors include insufficient vitamin B12 and genetic mutations in the MTHFR gene.  Methylenetetrahydrofolate Reductase (MTHFR) is a key enzyme required to metabolise homocysteine. The most common mutation in MTHFR is called C677T. People with two copies of this mutation are called homozygotes, and are found in 5-10% of the population. These individuals are predisposed to developing high blood levels of homocysteine, particularly when their diets are low in folate. A second mutation in the MTHFR gene called A1298C has also been implicated with high levels of homocysteine, when found together with the C677T mutation. MTHFR gene mutations found in individuals with other inherited clotting genes (eg Factor V Leiden) have a dramatically increased risk of venous thrombosis.

Warfarin Dose Predict

Warfarin is one of the most widely prescribed anti-coagulants today. It’s use is indicated in the prevention of thromboembolism, as well as the management of thrombotic disease (or blood clots).The selection of the correct initial warfarin dose has until recently, been determined empirically using both clinical and biochemical indicators, such as patients age, other medications and liver function. Despite this traditional approach to warfarin dosing considerable patient to patient variation is frequently seen, as assessed by the INR, and clinically, by the complication of bleeding when the initial dose is set too high. Therefore, predicting a patients standard warfarin dose remains sub-optimal resulting in the potential for over anti-coagulation and hemorrhage.Recently, two liver enzymes were identified as key components of warfarin breakdown and activity. Genetic variants of these enzymes called CYP2C9 and VKOCR1have been found to be responsible for up to 50% of patient to patient variation in the response to standard warfarin doses.Indentifying these genetic variants in patients prior to warfarin dosing should lead to more accurate personalized doses and reduce the risk of serious hemorrhage.

BCR-ABL1

The BCR-ABL1 gene fusion is acquired when pieces of chromosome 9 and chromosome 22 break off and switch places. The resulting chromosome 22 that has the BCR-ABL1 gene sequence is known as the Philadelphia chromosome. The BCR-ABL1 gene encodes an abnormal protein that is responsible for the development of CML and a type of ALL. This abnormal protein drives uncontrolled growth of leukemic cells. At diagnosis, 90-95% of cases of CML show the characteristic t(9;22) BCR-ABL1reciprocal chromosomal translocation.

JAK2

The JAK2 V617F mutation is present in approximately 90% of polycythemia vera cases and approximately 40% of primary myelofibrosis or essential thrombocythemia. Mutation analysis helps differentiate reactive conditions from myeloproliferative neoplasms

 

Oncology

Somatic Mutation Testing in Solid Tumours

Molecular characterisation of solid tumours is now playing a central role in patient’s management. Australian Clinical Labs offers Comprehensive Tumour Somatic Mutation Gene Panels for cancer Patients that support treatment decisions and improve patients’ outcomes. This is a Next Generation Sequencing (NGS) testing panel designed to investigate multiple relevant actionable mutations in formalin fixed paraffin embedded tumour samples.

Somatic Mutation request form

Colorectal Cancer Gene Panel

Molecular characterisation of solid tumours
is now playing a central role in patient management. The Australian Clinical Labs Colorectal Cancer Somatic Mutation panel is a Next Generation Sequencing (NGS) testing panel designed to investigate multiple relevant mutations in formalin fixed paraffin embedded colorectal cancer samples. This panel detects mutations within oncogenes and tumour suppressor genes that are frequently mutated in colorectal cancer that can aid clinicians to select the most appropriate treatment for their patients. Genes sequenced in this panels are kRAS, nRAS, BRAF, PIK3CA, PTEN and AKT1.

Lung Cancer Gene Panel

Molecular characterisation of solid tumours is now playing a central role in patient management. The Australian Clinical Labs Lung Cancer Somatic Mutation panel is a Next Generation Sequencing (NGS) testing panel designed to investigate multiple relevant mutations in formalin fixed paraffin embedded colorectal cancer samples. This panel detects mutations within oncogenes and tumour suppressor genes that are frequently mutated in lung cancer that can
aid clinicians to select the most appropriate treatment for their patients. Genes sequenced in this panel are EGFR, kRAS, nRAS, BRAF, PIK3CA, MEK1, AKT1 & ERRB2.

Melanoma Gene Panel

Molecular characterisation of solid tumours is now playing a central role in patient management. The Australian Clinical Labs Melanoma Somatic Mutation panel is a Next Generation Sequencing (NGS) testing panel designed to investigate multiple relevant mutations in formalin fixed paraffin embedded colorectal cancer samples. This panel detects mutations within oncogenes and tumour suppressor genes that are frequently mutated in metastatic melanoma that can aid clinicians to select the most appropriate treatment for their patients. Genes sequenced in this panel are BRAF, nRAS and cKIT.

26 gene Trusight Tumour panel

Molecular characterisation of solid tumours
is now playing a central role in patient management. Australian Clinical Labs offers the Illumina’s TruSight Tumour Somatic Mutation panel. This is a Next Generation Sequencing (NGS) testing panel designed to investigate multiple relevant mutations in formalin fixed paraffin embedded tumor samples. This panel detects mutations within 26 oncogenes and tumour suppressor genes that are frequently mutated in solid tumours that can aid clinicians to select the most appropriate treatment for their patients. The assay uses targeted NGS on an Illumina MiSeq instrument. Average amplicon coverage is >x2000 with an acceptance criteria
being >x500.

EndoPredict

EndoPredict® is a multi-gene test for breast cancer patients.Using a specially developed procedure, EndoPredict provides physicians with information to devise personalized treatment plans for their breast cancer patients. The method is based on analysis of tumour genes in combination with the classical prognostic factors of nodal status and tumour size.I n contrast to older multi-gene tests, EndoPredict detects the likelihood of late metastases (i.e., metastasis formation after more than five years) and can thus guide treatment decisions for extended anti-hormonal therapy. Accordingly, therapy decisions backed by EndoPredict confer a high level of diagnostic confidence. EndoPredict was shown to accurately predict cancer-specific disease progression and metastasis in multiple clinical outcome studies with more than 2,200 patients.

EndoPredict Request

Tamoxifen Predict

Tamoxifen can be considered a prodrug that requires metabolism
to elicit its pharmacological activity. Evidence suggests that endoxifen, a secondary metabolite
of Tamoxifen, is mostly responsible for Tamoxifen activity. In fact, endoxifen is one hundred times more potent as an anti-oestrogen than Tamoxifen itself. CYP2D6 is the main enzyme that metabolises Tamoxifen to endoxifen. A number of commonly occurring gene variants have been identified
in the CYP2D6 gene that result
in clinically important changes to CYP2D6 enzyme activity. Approximately 10% of the Australian population have gene variants in their CYP2D6 gene that results in little or no enzyme activity. These individuals are known as poor metabolisers. As such, poor metabolisers may
not receive the full medical benefit
of Tamoxifen therapy

UGT1A1 (Irinotecan)

In July 2005, the FDA approved revisions to the safety labeling for Irinotecan-HCl injection to recommend reduced dosing in patients who are homozygous for the UDP- glucuronosyltransferase 1A1 (UGT1A1)-*28 allele. UGT1A1 conjugates
the active metabolite
of irinotecan, S-38 to a glucuronide metabolite. Its activity is reduced in patients with the variant allele UGT1A1*28. Homozygosity of this allele is found in 10% of the population.