Microsatellite Markers: includes a panel of 10 markers in norm and tumor
NR21, NR24, D2S123, D5S346, BAT25, BAT26, D17S250, BAT40, D18S58, TGFβRII, (Titano MSI kit, Diatech Pharmacogenetics) Bethesda panel
Basic characteristics of the clinical phenotype:
Lynch syndrome, also known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC; OMIM #120435), is a hereditary cancer syndrome that results from germline mutations in DNA mismatch repair (MMR) genes. They are responsible for the correction of small errors that occur in the DNA nucleotide sequence (mismatches) during DNA replication. Mutations in MMR genes lead to genomic instability, characterized by a reduction or increase in the number of tandemly repeated sequences (microsatellites).
The microsatellite instability (MSI) leads to the occurrence of somatic mutations in oncogenes and/or in tumor-suppressor genes and a molecular and biological changes that are associated with increased sensitivity to immunotherapy.
Lynch syndrome is characterized by an early onset and a very high risk of developing cancer, particularly in the right colon, but also in the endometrium, ovaries, stomach, bile ducts, kidneys, bladder, ureter, and brain. Each year, more than 500,000 new cases of colon cancer occur worldwide. MCH can also be observed in gastric, endometrial, ovarian, skin, brain and other tumors, but the most common cause of carcinogenesis is observed in colorectal tumors.
Indications for Referral/ Clinical Significance:
Candidates for this test are all patients who strictly meet the revised Bethesda criteria (persons with carcinoma from families fulfilling the Amsterdam criteria; colorectal or uterine tumor with early onset
(before the age of 50); presence of synchronous, metachronous or other colorectal carcinoma, associated with HNPCC, regardless of the age of onset; CRC with a high degree of microsatellite instability (MSN) in patients under 60 years old; Persons with CRC in at least one first-generation relative of HNPCC-associated tumor, with tumor onset before the age of 50 years old.
Individuals with CRC in at least two first- or second-generation relatives with HNPCC – associated tumor, regardless of the age of onset).
Clinical characteristics of Lynch syndrome, defined by Amsterdam II criteria, include hereditary colorectal (Type I) or extracolonic (Type II) tumor in at least three relatives within at least two consecutive generations, with age of onset before 50 years old in at least one of the relatives, and excluding cases of familial adenomatous polyposis (FAP). The tumor must be histologically verified.
Interpretation of results:
MSN is a good diagnostic marker in identifying patients with Lynch syndrome, with no prognosis for the development of metastases and less aggressive treatment regimens.
MSN is a good prognostic marker of the response to targeted immunotherapy.
Patients with tumors showing a low degree of MS were classified as tumors with an alternative to Lynch syndrome etiology.
Patients with tumors with high degree of MSN are characterized by a better prognosis compared to those with tumors showing a low grade of MSN and microsatellite stability.
Patients with tumors showing a high degree of MCH are suitable for the testing of germline mutations in MMR genes - MLH1, MSH2, MSH6 and PMS2 or the promoter methylation status of MLH1 and MSH2 genes.
The genetic counselor will interpret and answer all questions about your result.
Method: DNA fragment analysis (Titano MSI kit, Diatech Pharmacogenetics) Bethesda panel
Sensitivity of the method: 82 %
What does the test involve?
· DNA isolation and sample storage.
· Polymerase chain reaction of the tested markers.
· DNA fragment analysis
· Forming a written result of the genetic test.
· Diagnostic interpretation of results and genetic counseling.
Biological material:
Venous blood or DNA isolated from venous blood
Fresh or FFPE tumor tissue or DNA isolated fom fresh or FFPE tumor tissue.
For more information, please read the "Biological material requirements and shipping information" carefully.
