We work with Asper Biotech company, which performs genetic tests for colorectal cancer, breast and ovarian cancer, lung cancer, glioblastoma, and cancer-associated symptoms.
We offer to do the tests quickly, so that the diagnosis and risk of the disease can be determined as soon as possible. Early diagnosis of cancer is important to improve the outcome of treatment and prolong life.
The basic method is based on the sequencing approach, including the sequencing of the younger generation, which allows disease mutations and changes in genes to reveal accurately and with a high degree of reliability.
In special cases, APEX (arrayed-primer extension) and MLPA (multiplex ligation-dependent probe amplification) tests are used.
The following tests are available:
- BRAF gene mutation analysis
- Definition of pre-exposure to breast and ovarian cancers
- Definition of familial adenomatous polyposis (FAP)
- Definition of Lynch syndrome / hereditary colon cancer without polyposis (HNPCC)
- Definition of Lynch syndrome and polyposis syndrome
- Determination of microsatellite instability (MSI)
- MUTYH - definition of associative polyposis (MAP)
- Determination of thiopurin-S-methyltransferase (TPMT) deficiency
- Sequencing of exome
Analysis of BRAF gene mutation
The BRAF gene encodes serine / threonine kinase, which functions via Ras-Raf-MEK-MAPK, which connects extracellular signals with a transcriptional regulation route. Activated mutations of BRAF are found in cases of colorectal cancer, melanoma, ovarian cancer, lung cancer and thyroid gland. The most common BRAF mutation is c.1799T> A (V600E); this mutation creates a predisposition to inhibition of apoptosis, increases invasiveness of the tumor and occurs during carcinogenesis.
Indications for the analysis of this mutation:
1) Determination of BRAF mutation can be used to identify cases of sporadic MSI-H (high microsatellite instability) of colorectal cancer, thus excluding mutation in mismatch repair genes. BRAF V600E mutation in colorectal cancer occurs in more than 90% of all BRAF mutations, and there are 30-80% of sporadic MSI-H colorectal cancer. This mutation is very rare in tumors that are associated with Lynch syndrome. The mutation BRAF V600E is closely associated with sporadic colorectal cancers, which are characterized by MSI (microsatellite instability) due to inactivation of somatic expression of the MLH1 protein. If the BRAF V600E mutation or MLH1 promoter methylation is detected in the case of the MSI-H tumor, the tumor is most likely sporadic, so further testing for confirmation of Lynch syndrome is not necessary.
2) BRAF mutation is an independent sign of a response to EGFR (epidermal growth factor receptor) in patients with inhibitory colorectal cancer. BRAF mutations create resistance to anti-epidermal therapy of epidermal growth factor in patients with colorectal cancer, so the presence of BRAF mutations is an important biomarker for deciding on the correct treatment tactics (use of anti-EGFR medications).
3) Determination of the presence of mutations BRAF can be used to determine the tactics of therapy for patients with melanoma. BRAF mutations are found in 70% of cases of primary melanoma. BRAF V600E kinase inhibitors are available for melanoma therapy, but their use is limited to patients with melanoma metastases and the proven mutation BRAF V600E.
Breast and ovarian cancer
Breast and ovarian cancer is associated with mutations in the BRCA1 and BRCA2 genes. In women who have a clinically significant mutation of BRCA genes, the risk of developing breast and / or ovarian cancer is 80%. The mutations BRCA1 and BRCA2, responsible for cancer, in genes originate autosomal dominant way. The viability of breast cancer depends on the stage at which it was identified, and therefore the timely identification of mutations is important.
Indications for genetic testing:
1) The test is performed if the breast or ovarian cancer in the patient manifests at an early age.
2) The test is carried out on patients whose families have already detected breast or ovarian cancer.
3) The test is carried out by patients whose relatives have already proven a mutation of these genes.
4) The test should be carried out if a family history of breast or ovarian cancer cases is identified, genetic mutations or breast cancer are identified in any of the men in the family.
Predisposition to cancer
Determining the predisposition to cancer is important to be able to diagnose diseases in the early stages and, possibly, avoid it. Early detection of cancer provides a timely start to treatment, which is critical in order to improve vitality and recovery. The difference in length of life, depending on whether the diagnosis of cancer is diagnosed early or late, is the main argument why it is necessary to assess the likelihood of developing cancer.
Identification of genetic predisposition to congenital cancer syndromes allows to start implementation of strategy in the field of risk reduction, calculate the risk of cancer in the family and identify family members who are at risk.
In determining the predisposition to cancer, tests of the newest generation based on DNA sequencing are used. Thus, a simultaneous analysis of several genes that are associated with an increased risk of cancer.
Indications for genetic testing:
1) The test is carried out in patients with a malignant tumor that manifests at an early age.
2) The test is carried out in patients with multiple primary malignant tumors.
3) The test is conducted for those people whose relatives have a malignant tumor.
4) The test is carried out for those people whose family history makes you think of a congenital malignant tumor, but genetic changes have not been ascertained before.
Family adenomatous polyposis
(FAP – Familial Adenomatous Polyposis)
Family adenomatous polyposis is a syndrome of pre-disposition to colon cancer, which is characterized by the appearance of hundreds and thousands of adenomatous polyps throughout the large intestine at an early age. At the age of 35 years, 95% of patients with familial adenomatous polyposis have polyps. If a patient with this syndrome is not treated, colorectal cancer develops at the age of 35-40 years. Polyposis, associated with cancer of adenomatous polyps, is inherited in an autosomal dominant manner.
Indications for the analysis of this mutation:
1) The test is performed in patients with adenomatous polyps.
2) The test is carried out by people whose first-degree relative is diagnosed with this disease.
Lynch syndrome / Herniated nonpolyposis colorectal cancer (HNPCC)
Lynch syndrome, also known as gereditic non-colitisectal colorectal cancer (HNPCC), is associated with an increased risk of colon cancer and other malignant tumors (eg, endometrial, ovarian, stomach, small intestine, hepatobiliary, upper urinary tract, brain and skin cancer ).
Lynch syndrome is inherited in an autosomal dominant fashion, associated with mutations in gametes, and more specifically in the corrective genes of DNA strands (MMR genes) - MLH1, MSH2 and MSH6 PMS2. Carriers of a mutation during life have a high risk of developing any of the above listed cancers, but the risk of development of colorectal cancer (80%) and endometrial cancer (20-60%) is especially high. A typical symptom of Lynch syndrome is its manifestation at an early age, that is, the diagnosis is established on average at the age of about 45 years.
Tumor tissue analysis is performed in patients who have confirmed the criteria of Amsterdam II or Bethesda to detect the expression of MMR proteins using immunohistochemical (IHC) analysis and microsatellite instability (MSI) DNA.
If expression of MLH1 / PMS2 proteins with IHX is not found, methylation of MLH1 gene promoters and / or somatic determination of BRAF V600E mutation is recommended to exclude other genetic causes of sporadic colorectal cancer.
If a tumor with a deficiency of MMR proteins and a pronounced instability of DNA microsatellite is detected, further analysis of the mutation of the MMR gene in peripheral blood and normal tissues is indicated.
Indications for mutation analysis:
1) The test is performed for patients who meet the criteria of Amsterdam II or Bethesda.
2) The test is carried out in patients who had a family history of colorectal cancer or cancer associated with Lynch syndrome.
3) The test is performed for patients who are at high risk of developing cancerous cancers, since relatives have confirmed any of the above mutations.
Instability of microsatellites - MSI
Microsatellite instability is the type of mutation that arises in the case of colorectal cancer. These mutations inactivate genes that participate in the process of correcting DNA errors (mismatch repair genes - MMR genes). If there are defects in these genes, the cell DNA accumulates somatic mutations, resulting in the cells becoming malignant. If this gene mutation is formed along the gamete line, they can be passed on to the next generation; such a transmission mechanism is characterized by heterodial non-lupous cancer (HNPCC). In families in which colorectal cancer is characteristic and Amsterdam's criteria are confirmed, in about 90% of cases microsatellite instability (MSI) is detected.
Polyposis associated with MUTYH (MAP)
Polyposis associated with MUTYH (MAP) is an autosomal recessive disease characterized by the appearance of a different amount of colorectal adenomas; these adenomas have a high risk of developing colorectal cancer. MAP causes biallelic mutations of the MUTYH gene in gametes, but there are reports that the carriers of monoallelic mutation have an increased risk of developing colorectal cancer. The clinical symptoms of MAP often do not differ from familial adenomatous polyposis (FAP) or attenuated familial adenomatous polyposis (AFAP), which are caused by mutations in the adenomatous polyposis (APC) gene, but compared with FAP, polyposis associated with MUTYH is more pronounced in elderly patients . For representatives of the white race, two mutations are characteristic that are responsible for 80% mutant alleles in the case of polyposis associated with MUTYH; these are the mutations p.Y179C and p.G396D (also known as Y165C and G382D).
Indication for genetic examination:
1) The test is conducted to clients with clinical symptoms that are similar to FAP or AFAP, but who do not have a fixed mutation in the APC gene;
2) In the case of a confirmed mutation, the test is conducted to relatives of the first degree of the patient.
Deficiency of thiopurin-S-methyltransferase - TPMT
Such medications containing thiopurine, such as 6-mercaptopurine and azatoprine, are used as chemotherapeutic agents, and their active metabolites have both immunosuppressive and antiproliferative effects.
Thiopurine-S-methyltransferase (TPMT) is an enzyme that catalyzes the S-methylation process in preparations containing thiopurin and is involved in the synthesis of inactive metabolites. There are genetic polymorphisms that affect this enzymatic process and can be the cause of the toxicity of these medications, which can be life threatening. Bone marrow toxicity caused by medications can be detected as myelosuppression, anemia, leukopenia, infection, or coagulation disorders.
Indication for genetic examination:
1) The test is performed to determine the activity of the TPMT enzyme and select the optimal dose of medications before starting therapy. This test should be performed for those patients for whom medication with thiopurine is prescribed.
Exo sequencing
Exo sequencing involves the sequencing of protein-coding and complementary intron regions in about 20,000 genes of the human genome. The coding region represents approximately 1-2% of the human genome, but contains about 85% of the pathogenic mutations. Exo sequencing can be used as an effective tool for physicians to confirm a patient's diagnosis in very difficult cases, where confirmation can not be obtained using a standard genetic test.
Indications for genetic research:
1) The test is conducted to confirm the clinical diagnosis;
2) The test is conducted to establish a diagnosis of genetic disease in patients in whom this is not possible using standard diagnostic panels;
3) The test is conducted to identify the genes that caused the disease.
