Endocrinology and Metabolic Diseases

MODY (Maturity Onset Diabetes of the Young) is a rare form of diabetes, different from Type I and Type II diabetes. It is an autosomal dominant disease with low prevalence and genetic heterogeneity. It emerges before the age of 25, independently of factors such as ethnic group, nutrition and weight. Of the types defined so far, it is recommended to study, in order, MODY type 2: GCK (glucokinase), MODY type 3: HNF1A (hepatocyte nuclear factor-1 alpha), MODY type: HNF4A (nuclear factor-4-alpha), MODY type 5: HNF1B (hepatocyte nuclear factor 1 beta).

Tumors leading to multiple endocrine neoplasia (MEN) syndromes originate from neuroendocrine APUD cells. All show autosomal dominant transmission. There are 3 MEN syndromes in addition to non-syndromic medullary thyroid cancer (MTC). MEN 1 is a very rare disease. Its prevalence is between 0.02 and 0.2 per thousand people. MEN-1 is characterized by hyperplasia or adenoma of the parathyroid glands, and involvement of the pancreatic islets and pituitary gland. Other tumors defined in MEN 1 are vipoma, glucagonoma, somatostatinoma and PPoma. The MEN-1 gene is on the long arm of chromosome 11 and is probably a tumor suppressor gene.

50% of cases with familial breast cancer result from BRCA gene mutations. Approximately 33% of women with breast cancer observed under the age of 30 are carriers of one of these mutations. Ovarian cancers rank 5th in cancer deaths in women. 5-10% of these have a family history and frequently result from BRCA1 and BRCA2 mutations. In women who have inherited a mutation from the family, the risk of developing breast and ovarian cancer is significantly increased compared to the general population. In the presence of a BRCA1 mutation, this risk is 85% and 45% for breast cancer and ovarian cancer, respectively; in BRCA2 mutations, an increased breast cancer risk similar to BRCA1 mutations is observed, and this risk is 27% for ovarian cancer.

In patients negative for BRCA gene mutations, the HBOC panel is recommended:

Although each tumor has its own distinctive characteristics, molecular disorders most often lie in known pathways. Unknown somatic mutations are rarely seen in profiling tumor types. Hotspot mutations occurring in DNA segments encoding certain protein domains can be given as an example. Hotspot regions are very important in genetic diseases. Because these regions are hot spots and their mutation rates are much higher compared to other regions. And studies on recurrent mutations in these regions can offer us valuable information. It is thought that these may lead to the discovery of new drug treatments for cancer types.

Inactivation of tumor suppressor genes (TSG) can cause cancer predisposition and the emergence of familial cancer syndromes. Mutations in TSGs are passed on to subsequent generations through germ cells. These mutations initially occur in the germline, in sperm or egg cells, and are inherited by the person to be born. It should not be forgotten that while the inherited mutant TSG causes a serious increase in risk for cancer predisposition, an inherited mutant TSG is not at the basis of all familial cancers.

TSGs become inactive after mutations occur in both alleles, losing their suppressor effects on cell proliferation. More rarely, two mutations can be observed in a TSG inherited normally from the mother and father during life, provided they are in the same cell. However, in a person who has inherited one of the mutations from their family hereditarily and carries it in all their cells, the occurrence of a second mutation and the consequent development of cancer is much more likely due to the abundance of affected cells.

The absence or functional disorder of any of the elements that make up our immune system is called immunodeficiency diseases. When these diseases develop due to hereditary or genetic causes, they are called primary immunodeficiency (immune system deficiency). A very large number of primary immunodeficiency types have been defined so far.

More than 200 genes are examined within the scope of the panel. You can contact our center for the comprehensive gene list.

What is Familial Mediterranean Fever (FMF)?

It is an autosomal recessive inherited disease characterized by recurrent fever and inflammation attacks of the synovium, peritoneum or pleura, accompanied by pain. Attacks accompanied by fever and abdominal pain, in which spontaneous recovery is observed, are typical. Renal failure due to amyloidosis is the most serious complication of the disease. The disease is observed especially in Turkish, Armenian, Arab and non-Ashkenazi Jewish communities. In these communities, the disease frequency is 1/200 and carrier status is 1/5. Since it can be confused with abdominal diseases, making the genetic diagnosis of the disease will prevent the patient from being exposed to unnecessary surgical operations.

Colon cancers are among the most common cancer types in the world. According to the statistics of the Ministry of Health, colon (large intestine) cancer is also among the 5 most common cancer types in our country. Although colon cancer has a risk of occurring at any age, it is most frequently observed after the age of 50. When the distribution by gender is examined, colon cancer ranks second among all cancers in women and third in men.

A person whose family has previously had colorectal cancer has a higher cancer risk. Hereditary genetic factors increase the risk ratio. Both familial adenomatous polyps in the large intestine and hereditary non-polyposis colorectal cancer, also known as Lynch syndrome, increase the risk of colon cancer. Although genetic colorectal cancers constitute only 5-10% of the disease, people carrying these genetic factors are younger at the age of onset than other colon cancer patients and carry greater vital risk.

There are also solutions for solid tumors and hematological oncology, aimed at providing advanced genomic analysis with accurate and sensitive methods in cancer samples. Panels designed to accurately detect simple and complex genetic mutations from low nucleic acid materials obtained from FFPE, fresh tissue and blood samples using the New Generation Sequencing (NGS) method allow DNA, RNA and ctDNA sequencing in different tumor types. DNA-based panels target SNV, Indel and CNV variant types, while RNA-based panels perform fusion (translocation) and expression detection.

• The molecular profiling test in adult cancers is a targeted next-generation sequencing (NGS) test that enables the detection of single nucleotide variants (SNVs), copy number changes (CNVs), gene fusions and indels from 161 genes.
• It performs a highly specific mutation profiling by analyzing some genes as hot-spots, some by sequencing the entire exome, and others by looking at copy number changes.
• This test can be run with as little as 10 ng of DNA or RNA obtained from formalin-fixed paraffin-embedded (FFPE) samples. This allows even low-amount FFPE samples to be analyzed.
• It offers a unique method for planning personalized cancer diagnosis and treatment.
• It is created as a result of mutations detected with quantitative analysis methods using AmpliSeq technology being analyzed with Ion Reporter Software and prepared as a PERSONALIZED REPORT.
• The report content includes the mutation-treatment relationship, drug studies, clinical trials and the relevant literature.

• In immuno-oncology research; immunotherapy is now accepted as a fundamental component of oncology therapeutic strategies.
• The aim is to use the body's own immune system to recognize, control or potentially eliminate cancer.
• Immunotherapy has the potential to influence a clinical treatment outcome or transform cancer from a fatal disease into a non-life-threatening or chronic disease.
• Tumor mutational burden (TMB), a measure of the number of mutations in a tumor genome, is a biomarker evaluated by whole exome sequencing (WES). In recent studies, it shows high concordance with WES.
• Tumor Mutational Burden measures biomarkers and explains the state of the relationship between TMB and future therapeutic response in various cancers.