PreciONC - ONCOLOGY
One of the world’s leading causes of death is cancer and one million new cancer cases are identified, and millions of people die every year from this deadly disease. The small silver lining of the whole sad problem is that if cancer is diagnosed in time, millions of individuals will be saved.
The New Era – Instead of treating tumors with the same blanket chemotherapies, there are more intelligent approaches that allows the features of the tumors to precisely match the drugs that will target the tumors selectively this is the basis of Precision Oncology
Critical requirement is that Tumors be assessed for the presence of mutations, genetic aberrations or transcriptome analysis.
Precision Oncology – Treatment Tailored to Individual Characteristics of each patient’s disease. More efficient, Less Toxic.
BioServe Biotechnologies continuous efforts to provide clinicians with an integrated molecular diagnostic solution for Oncology allows hereditary risk assessment, differential diagnosis, reliable prognosis, selection of targeted treatment, monitoring of therapy, and surveillance of disease.
Genetic testing helps predict your risk of developing cancer. By looking for subtle changes in the genes, chromosomes, or proteins, genetic testing helps to find out the variations and these variations are called as “Mutations”.
Our Cancer Panels
Pharmacogenomics uses knowledge about the genetic makeup or genome of a person to pick the drugs and doses of drugs that are likely to function best for that specific individual. The study of how medicines function, called pharmacology, blends this new discipline called genomics and this term collectively called as Pharmacogenomics.
Some drugs can work for you efficiently than they do in other individuals, depending on your genetic makeup. Similarly, some drugs in you can cause side effects than in someone else.
We help Doctors to choose the right drug to stop the trial-and-error method of offering you multiple medications that are not likely to work for you until they find the correct one by using knowledge about your genetic make-up. The “best-fit” drug to assist you can be picked from the beginning using our pharmacogenomics panels.
- DPYD testing for Treatment with 5-fluorouracil treatment (10 Variants)
- UGT1A1 for Irinotecan therapy (3 variants)
- Glioblastoma IDH1 and IDH2 Mutations
- EGFR mutation detection in exon 18,19,20,21 in NSCLC for treatment with EGFR TKIs
- Detection of T790M in EGFR in non-small-cell lung cancer (NSCLC)
- Variants in PIK3CA (Exon7, 9, 20)
- Detection of BRAFV600E and V600K mutations in Melanoma
- Detection of ABL Kinase mutations for drug response (Exon 4, 5, 6,7)
- Detection of variants in TPMT (TPMT2*, TPMT3A*TPMT3C*)
DPYD testing for Treatment with 5-fluorouracil treatment (10 Variants)
An enzyme known as dihydropyrimidine dehydrogenase (DPYD) is encoded by the DPYD gene. This enzyme is important for the metabolism of fluoropyrimidine drugs including fluorouracil/5-FU and capecitabine. For certain cancers, including head and neck, gastrointestinal and colorectal cancers, these medications are all part of chemotherapy treatment. As a result of reduced DPYD activity, mutations or variations in DPYD are known to cause significant 5-FU toxicity. Before beginning their treatment protocol, patients who are candidates for therapy with fluorouracil or capecitabine should be considered for DPYD genotyping, especially if the patients have a personal or family history of 5-FU toxicity.
UGT1A1 for Irinotecan therapy (3 variants)
UGTs play a major role in the conjugation and subsequent elimination of xenobiotics and endogenous compounds which are potentially toxic. A hepatic enzyme responsible for bilirubin conjugation encodes the UGT1A1 gene. It also acts on the active metabolite, the primary cause of treatment-related toxicity of chemotherapeutic agents including irinotecan, which is used in the treatment of colorectal and gastric cancers. The lengths in the promoter region of the UTG1A1 gene of the repeat polymorphism are determined using Sanger Sequencing by fragment analysis.
Glioblastoma IDH1 and IDH2 Mutations
In around 15-20 % of acute myeloid leukaemia (AML), IDH1 or IDH2 mutations are observed and grade II or III brain gliomas of > 70 percent. It is possible that patients with AML and mutations aggressive cancer, while glioma mutations are associated with improved prognosis. For patients with IDH1, long term survival after aggressive tumour resection has been confirmed beneficial astrocytomas. Bi-directional sequencing in both IDH1 and IDH2 of the hotspot regions of the exon 4 mutation. Genes IDH1 and IDH2 are analysed simultaneously. Testing can be done for haematological diseases to boost sensitivity which is being performed on plasma.
EGFR mutation detection in exon 18,19,20,21 in NSCLC for treatment with EGFR TKIs
There are mutations in the EGFR gene in about 25 % of non-small cell lung cancers (NSCLC). Most mutations in exons 18, 19, 20 and 21 occur in hotspot areas. Epidermal growth factor receptor (EGFR) gene mutations are biomarkers that predict how patients with non-small cell lung cancer (NSCLC) react to EGFR-targeted therapies known collectively as tyrosine kinase inhibitors (TKIs). EGFR genotyping therefore offers essential details for the decision on treatment. For EGFR genotyping Sanger sequencing is employed to identify the mutations in the exon regions.
Detection of T790M in EGFR in non-small-cell lung cancer (NSCLC)
The most common cause of death from cancer worldwide is lung cancer, there is non-small cell lung cancer (NSCLC) and 85-90 % of lung cancers. Presence of the epidermal growth cell receptor (EGFR) gene-driver mutations in a subset of non-small cell lung cancer NSCLC. The use of tyrosine kinase inhibitors (TKI) that inhibit EGFR signalling has led to the use of the pathway.
The epidermal growth factor receptor (EGFR) gene has been identified as a non-small cell lung cancer (NSCLC) driving gene, and the efficacy of the EGFR-tyrosine kinase (TKI) inhibitor has been demonstrated, but acquired resistance is inevitable. The presence of T790M-mutation will recognise patients who are eligible for tyrosine kinase inhibitor (TKI) therapy.
Tumours that contain such EGFR mutations may have an initial response. EGFR-TKIs, however many develop post-treatment resistance mutations, also at exon 20’s amino acid position 790 (T790 M). Accurate detection of T790M in patients whose disease progressed on initial TKI therapy is thus vital for subsequent management.
Variants in PIK3CA (Exon7, 9, 20)
A significant cell signalling pathway mediating cell proliferation and survival is the phosphatidylinositol 3-kinase / AKT axis, two biological processes that control the growth of malignant cells. The p110α subunit of the phosphatidylinositol 3-kinase protein encodes the phosphatidylinositol 3-kinase CA gene. In some types of human tumours, there are phosphatidylinositol 3-kinase CA mutations, and they are commonly seen in breast cancer. In a broad variety of tumours, including glioblastoma, gastric cancer, lung cancer, ovarian cancer, hepatocellular cancer, endometrial cancer, brain cancer and breast cancer, this gene is mutated. Phosphatidylinositol 3-kinase CA mutations are associated with poor survival and may be useful biomarkers for the detection of aggressive tumour patients with breast cancer and for the prediction of response to PI3K pathway inhibitor therapy.
Detection of BRAFV600E and V600K mutations in Melanoma
In 7% of human cancers, BRAF mutations were detected. They are uncommon in certain tumours, such as myeloma (4%) and are present in 100% of hairy cell leukaemia. The prevalence of BRAF mutations in melanoma is 40% to 50% and depends on the form of melanoma. A substitution of glutamic acid for valine at codon 600 BRAF protein, is the most common mutation found in about 75% of all BRAF mutation-positive melanoma (V600E).
Detection of ABL Kinase mutations for drug response (Exon 4, 5, 6,7)
Chronic myeloid leukaemia (CML), the myeloproliferative disorders are better characterised and are associated with the development of myeloproliferative disorders in over 95% of the affected patients. The BCR-ABL1 is a fusion oncogene, the product of the chromosomal translocation of t(9;22)(9q34.1)(22q11.2). The BCR-ABL gene and the fusion protein that has the activity of constitutive tyrosine kinase result from this translocation. The key cause of resistance to tyrosine kinase (TKIs) in patients with chronic myeloid leukaemia is mutations in the BCR-ABL tyrosine kinase domain in 30% to 90% of patients who develop resistance. Imatinib is a highly effective therapy in all stages of chronic myelogenous leukaemia (CML), but relapse after initial response is normal in patients with advanced disease. BCR-ABL kinase domain (KD) mutations have been observed in 50 to 90 % of patients with acquired resistance to imatinib. These mutations result in impaired binding of drugs and are believed to trigger clinical resistance.
Detection of variants in TPMT (TPMT2*, TPMT3A*TPMT3C*)
A phase two drug-metabolizing enzyme produced in the kidney, red blood cells, liver, and other tissues is thiopurine methyltransferase (TPMT). In the removal of thiopurine medicines, like mercaptopurine, azathioprine and thioguanine, TPMT plays a function. These medicines are usually used to treat acute lymphoblastic leukaemia, autoimmune disorders, inflammatory bowel disease and rejection of organ transplants. There is intermediate TPMT operation in about 10 percent of the population.
Life-threatening myelosuppression, a disorder in which bone marrow production is reduced, and other toxicities may be caused by impaired TPMT function in patients given regular thiopurine doses. In infants, impaired function has also been associated with ototoxicity caused by cisplatin, although this is not well known. To tolerate therapy and reduce the risk of adverse reactions, individuals with reduced TPMT activity may require thiopurine dose reductions of 50 to 90 percent.
Solid tumors, as the name suggests, are solid masses devoid of fluids or cysts. Tumors that are solid may be either malignant or benign. Solid tumors may only have a different appearance than blood tumors but can also need a different treatment procedure. In the muscles, bone, and organs of the body, solid tumors may develop. Mesothelioma, sarcomas, lymphomas, sarcomas and cancers of the breast, prostate, kidney, ovary, pancreas, thyroid, and colon are examples. Solid tumors are categorized using grades based on the anomalies found in tumor cells by pathologists and how likely the tumor is to spread.
The risk of breast cancer may be increased by mutations in the BRCA1 and BRCA2 (breast cancer 1 and breast cancer 2) genes. BRCA mutations can be inherited, and an increased risk of developing cancer is associated with them. For individuals with a personal or family history of cancer, or for those with a particular form of breast cancer, the BRCA gene test is usually prescribed. Usually, the procedure is not carried out on people with an average risk of breast cancer.
BRCA 1 & BRCA 2 Mutation Analysis
BRCA1 & BRCA2 germline mutations cause inherited breast syndrome and account for about 5-10 % of all cases of breast cancer, and 90% of breast cancer in the family. Mutations impart increased early risk breast cancer, multiple primary breast cancer, male breast cancer, epithelial ovarian cancer, fallopian cancer. Mutations of the BRCA2 are also related to an increased risk of melanoma. In triple-negative breast cancer, the prevalence of the BRCA mutation is increased, especially among younger patients. Mutation prevalence is in the general population, about 1/300 for BRCA1 and 1/800 for BRCA2, with some groups with a higher incidence due to mutations of the founders. Genetic testing promotes therapy selection, preparation for monitoring, and identification of family members at risk.
This test is carried out by sequencing the entire genes of BRCA1 and BRCA2 using massive parallel sequencing, point mutation detection methodologies, small & large insertions / deletions and copy number variations.
Comprehensive Cancer Panel
The exons of 409 tumour suppressor genes and oncogenes commonly cited and frequently mutated are targeted by the Comprehensive Cancer Panel. Strategically designed to simultaneously analyse coding DNA sequences and splice variants across multiple gene families, our pathway-based gene selection processes the mutational continuum, along with signalling cascades, in cancer driver genes and drug targets. In a single assay, apoptosis genes, DNA repair genes, transcription regulators, genes for inflammatory response and growth factor genes.
- Wide survey of 409 primary genes in a simple reaction.
- Unmatched plexy with our technology of 16,000 primer pairs in four pools only.
- Low DNA input of only 40 ng DNA and short amplicons make FFPE samples and biopsies of needles.
- Rapidly launch detailed genomic studies with pre-designed primer pools.
- Simplify variant analysis and annotation with tools.
RNA fusion panel for Lung Cancer
The most prevalent cancer worldwide is lung cancer. In 2012, there were some 1.82 million new cases worldwide and 1.56 million deaths, representing about 20 percent of all cancers. In India, 6.9% of all new cases of cancer and 9.3% of all cancer-related deaths in both sexes are lung cancer, the most common cancer and cause of cancer-related mortality in men, with the highest recorded incidences.
Chromosome aberrations have been shown to play an important role in the initial steps of tumorigenesis, especially translocations and their subsequent gene fusions. The identification of gene fusions indicates the hope that personalized cancer care decisions will play an important role in the future. In fresh-frozen solid tumours from common cancers, through next-generation sequencing technology, several uncommon gene fusion events have been identified.
This research panel targets over 70 fusion transcripts and has a sensitivity of 1% and the key advantage over current technologies (namely multi-colour fluorescent in situ hybridization (FISH) and array comparative genomic hybridization (array CGH) is the simplicity of the technique and its associated labour savings, with only a 10ng input RNA requirement and five housekeeping genes as an internal quality control.
RNA fusion panel targeted gene list