Molecular Diagnostics

PANAMutyper™ EML4-ALK Screening Kit is the qualitative diagnostic test kit which is able to detect 16 different EML4-ALK fusion genes of tissue from non-small cell lung cancer (NSCLC) patients using peptide nucleic acid (PNA) probes in a real-time PCR system. The PANAMutyper™ EML4-ALK Screening Kit is intended as an aid for screening EML4-ALK fusion-positive NSCLC patients who would be sensitive for receiving ALK inhibitor therapy such as crizotinib.

Lung cancer is a metastatic cancer which the cancer cells are developed in the bronchial tubes or alveoli and grow along the blood vessel or lymphatic vessel. There are two types of lung cancer based on the sizes and shape of the cancer cell; non-small cell lung cancer (NSCLC) takes 75% and small cell lung cancer takes 25%. Usually, it is hard to find lung cancer in the early stage and is diagnosed as lung cancer when it is already progressed. So the prognosis tends to be bad. It is known that the patients with EGFR mutation show very high drug responses against EGFR tyrosine kinase inhibitor (TKI) such as Gefitinib (Iressa, AstraZenca) and Erlotinib (Tarceba, Roche). We expect that genotyping EGFR genes of the lung cancer patients enables predicting drug response before treatment and this will lead effective lung cancer treatment.

PANAMutyper™ ROS1 Screening Kit is the qualitative diagnostic test kit which is able to detect 20 different ROS1 fusion genes of formalin-fixed paraffin-embedded (FFPE) tissue, fresh tissues and biopsy tissues from non-small cell lung cancer (NSCLC) patients using peptide nucleic acid (PNA) probes in a real-time PCR system.

The PANAMutyper™ ROS1 Screening Kit is intended as an aid for screening ROS1 fusion-positive NSCLC patients who would be sensitive for receiving ROS1 inhibitor therapy such as crizotinib, Lorlatinib, etc.

CML (Chronic myelogenous leukemia) patients who has consistently treated with Imatinib (Gleevec), have acquired point mutations in tyrosine kinase domain of BCR-ABL fusion gene. Especially, T315I mutation is known as a mutation associated with Imatinibresistance and observed with high frequency.
It is important to monitor patients treated with Imatinibby BCR-ABLfusion gene mutation test to prevent therapy failure due to drug resistance by mutation.

BRAF mutation is found in several cancers including thyroid cancer, malignant melanoma, ovarian cancer, colorectal cancer. In case of thyroid cancer, there are over 40 different types of BRAF mutation. Of these mutations, the V600E mutation on exon 15, i.e. change of nucleotide from T to A in 1799th base that results in change from valine to glutamate in amino acids, is most important with over 90% of frequency. Especially, BRAF V600E mutation is detected with ca. 45% of frequency in papillary thyroid carcinoma and is considered a prognostic maker for thyroid cancer.

Mutations of IDH1 (isocitrate dehydrogenase 1,IDH1) can be found in glioblastoma and myeloproliferative neoplasm. Detection of IDH1mutations can be a positive predictor of a prognosis and a molecular marker for glioblastoma patients. On the other hand, it is reported that IDH1 mutations correlate with poor prognosis in myeloproliferative neoplasm.
PNAClamp™ IDH1 Mutation Detection Kit is a new member of somatic mutation detection kits utilizing PNA-mediated PCR Clamping technology, and can help patients choose the right medicine and monitor prognosis.

IDH2 is frequently mutated in glioma, acute myeloid leukemia, and myelodysplastic syndromes. Mutations generally involve point mutations at the R140 and R172 residues of the protein. Mutations in IDH1 and IDH2 result in deleterious “gain of function”: instead of converting isocitrate to α-ketoglutarate, mutated IDH1 or IDH2 converts isocitrate to 2-hydroxyglutarate. 2-hydroxyglutarate inhibits other proteins involved in epigenetic regulation.

JAK2 V617F mutation is found in patients with blood related disease such as Polycythemia Vera, Essential Thrombocythemia and Myelofibrosis. Ruxolitinib is effective as a JAK Inhibitor, so that it is a prognostic factor to determine drug response.
JAK2 V617F mutation detection makes easy to classify patients with MPD (Myeloproliferative Disease) as three levels of diagnostic certainty (possible, probable and definite) and to determine which signal transduction therapy is suitable for each patients. In addition, testing for JAK2 V617F mutation has been recommended as clinical tests by WHO(World Health Organization).

PIK3CA mutation activates PI3K (Phosphatidylinositol 3-kinase) protein and PI3K activates several signaling pathways of tyrosine kinase receptors. Activated tyrosine kinase represses the function and excitometabolism of protein which inhibits cell survival and division. These abnormal changes initiate the process of cancer development by activating the protein involved in cell growth. Point mutations in PIK3CA are detected with ca. 80% of frequency in exon 9 (interpreted as helical part of PI3K protein) and exon 20 (interpreted as kinase part), while other types of mutations are also seen in many different locations. PIK3CA mutations are found with 25 to 40 % frequency in various types of cancer like colorectal cancer, gastric cancer, lung cancer, brain cancer, endometrial cancer, ovarian cancer, breast cancer, and more.

PNAClamp™ PIK3CA Mutation Detection Kit utilizes modified PCR technology, using optimized PNA probes that tightly bind to wild type DNA templates. This tight binding to the wild type DNA templates result in no amplification of the wild type DNA template in PCR reaction while the mutated genes, especially with SNPs, PCR amplification is processed for multiplication of the mutated DNA sequences.

The presence of TERT mutation is a prognostic and predictive biomarker in patients with cancer such as the central nervous system, bladder, thyroid, skin, etc., associated with tumor recurrence and survival.

With its features of detection limit as low as 5% copies/rxn, the PNAClamp™ TERT Mutation Detection Kit is the qualitative diagnostic test kit which is able to detect 2 different types of TERT promoter mutations of formalin-fixed paraffin-embedded (FFPE) tissue, fresh tissues and biopsy tissues using peptide nucleic acid (PNA)-mediated real-time PCR clamping technology.