Diatech Pharmacogenetics presents two products groups for anti-cancer therapy:
Pyrosequencing technology in pharmacogenetics of anti-EGFR therapy
Pyrosequencing technology in pharmacogenetics of chemo and radio therapy
Prior amplification with end-point detection of the human genomic DNA extracted from the cancer tissue (somatic pharmacogenetics) or from the peripheral blood (germinal pharmacogenetics), genotyping of each single mutation is performed by Pyrosequencing tecnology.
Main characteristics of the Diatech Pharmacogenetics kit on Pyrosequencing ID platform:
- SNPs analysis, insertion and deletion with ? accuracy.
- Polymorphism and its neighbourhood sequence detection.
- Automated genotyping of up to 96 samples in less that 30 minutes.
- Easy to perform and to interpretate the results.
The products of the lines Anti-EGFR moAb response® and EGFR TKI response® are the only CE-marked IVD kit capable of detecting, by pyrosequencing and in a simple and reliable way, the main mutations of the following genes:
- KRAS (codons 12, 13, 59, 61, 117, 146)
- BRAF (exons 11 e 15)
- NRAS (codons 12, 13, 59, 61, 117, 146)
- EGFR (exons 18, 19, 20, 21)
The kit Anti-EGFR moAb response® and EGFR TKI response® allow you to customize therapy with anti-EGFR monoclonal antibodies (cetuximab and panitumumab) and tyrosine kinase inhibitors (erlotinib and gefitinib), respectively.
In physiological conditions, the isocitrate dehydrogenase IDH1 and IDH2 are involved in many metabolic processes such as lipid synthesis, the cellular defense to oxidative stress, oxidative respiration and signal transduction.
Mutations in the IDH1 gene and, less frequently, the IDH2 gene have been reported in over 75% of the second and third grade gliomas and secondary glioblastomas and other tumors which do not affect the central nervous system : the subtype of acute myeloid leukemia with normal karyotype, thyroid cancer, the tumor cartilage, the intrahepatic cholan – giocarcinoma and occasionally prostate cancer, acute lymphoblastic leukemia of B cells and paraganglioma.
IDH1 and IDH2 mutations are mutually exclusive and are represented by the substitution of a singol amino acid, localized in the active site of the enzyme: the R132 of IDH1, or the analogous residue R172 of IDH2.
IDH mutations are closely associated with methylation of the MGMT promoter and represent a marker as strong as independent favorable prognosis in cases of glioma . All patients with mutated IDH1 or IDH2, in fact, show a higher survival than patients with wild-type IDH . Mutational analysis of IDH1 / 2 is very useful for the differential diagnosis of glioblastomas primary and secondary nutrients, which the histopathological point of view are not distinguishable, but from the clinical point of view represent two distinct subtypes of glioma grade IV, which develop different ways and show different prognoses. Moreover, the presence of IDH1 or IDH2 mutated in astrocytomas disseminated allows to distinguish these from astrocytoma pilocytic gliomas and ependymomas by, that have similar histopathological features.
The kit ” IDH 1/2 ® status ” allows you to identify, using Pyrosequencing, the main somatic mutations of the gene IDH1: R132H, R132L, R132C, R132G , R132S, and gene IDH2 : R172M,R172T,R172K,R172W,R172G,R172S.
The combined use of the kit IDH 1/2 status (code UP045 ) for mutational analysis of IDH1 and IDH2 and the kit MGMT plus (code UP050 ) for the analysis of the degree of methylation of MGMT allows to obtain important information on the diagnosis and prognosis of glioma.
The kit MGMT plus® allows to evaluate by pyrosequencing the methylation status of the MGMT promoter, which is an important predictor of response to temozolomide for the glioblastoma.
The quantitative analysis of the % of methylation of each of the ten islands in the region CpGlocalizzate chr10: 131,265,507-131, 265.556, made possible by the kit, is a valid aid to the personalized therapy of glioblastoma with alkylating agents.
The kit MGMT plus® is the first kit is used to measure methylation of MGMT containing all of the reagents for the treatment of DNA with bisulfite and two positive controls respectively constituted by methylated DNA and not for the monitoring of the analytical procedure starting from the conversion.