[The structure of pathogenic germline variants in colorectal cancer in Moscow patients]. / Struktura patogennykh germinal'nykh variantov pri kolorektal'nom rake v vyborke patsientov Moskvy.

OBJECTIVE: Describe the structure of pathogenic germline variants and clinical and anatomical features in colorectal cancer patients in Moscow. MATERIAL AND METHODS: The whole genome sequencing results of patients with suspected hereditary cancer syndrome were evaluated. All identified genetic variants were validated using Sanger sequencing. RESULTS: The study included 238 patients with colorectal cancer, 41/238 (17.2%) patients have pathogenic germline variants associated with hereditary cancer syndromes or increased cancer risk. Lynch syndrome accounts for 8% of all colorectal cancer cases (19/238), and familial adenomatous polyposis - 1.7% (4/238). 5 new genetic variants were described for the first time in a Russian colorectal cancer patients: MLH1 c.1921dup (p.Leu641fs), APC c.2929C>T (p.Gln977Ter), PMS2 c.327del (p.Ala110LeufsTer2), MSH2 c.1857dup (p. Val620CysfsTer24), ATM c.895G>T (p.Glu299Ter). In 197 of 238 patients, no significant variants were identified or variants with an uncertain clinical underlying cause were identified. CONCLUSION: According to the results of the study, an earlier manifestation of a malignant neoplasm and a more frequent occurrence of high-grade carcinomas in the presence of pathogenic germline mutations were noted compared to the group of patients without clinically significant varianrs, while in the group with identified mutations, the frequency of regional and distant metastasis was not increased.

[Landscape of KRAS, BRAF, and PIK3CA Mutations and Clinical Features of EBV-Associated and Microsatellite Unstable Gastric Cancer].

Personalization of gastric cancer (GC) treatment is an urgent problem because of the clinical heterogeneity and aggressive course of the disease. Four GC subtypes were isolated based on molecular characteristics by The Cancer Genome Atlas researchers in 2014: Epstein-Barr virus positive (EBV^(+)), microsatellite unstable (MSI), chromosomally unstable (CIN), and genomically stable (GS). There is no unified method to detect the CIN and GS subtypes today, while MSI and EBV status assessments are used routinely and are of great clinical importance. A total of 159 GC samples were tested for MSI, EBV DNA, and somatic mutations in codons 12-13 (exon 2), 61 (exon 3), and 146 (exon 4) of the KRAS gene; codons 597-601 (exon 15) of the BRAF gene; and codons 542-546 (exon 9), 1047-1049 (exon 20) of the PIK3CA gene. EBV^(+) GC was detected in 8.2% of samples; and MSI, in 13.2%. MSI and EBV+ were found to be mutually exclusive. The mean ages at GC manifestation were 54.8 and 62.1 years in patients with EBV^(+) and MSI GCs, respectively. EBV^(+) GC affected men in 92.3% of cases, 76.2% of the patients were older than 50 years of age. Diffuse and intestinal adenocarcinomas were diagnosed in 6 (46.2%) and 5 (38.5%) EBV^(+) cases, respectively. MSI GC equally affected men (n = 10, 47.6%) and women (n = 11, 52.4%). The intestinal histological type was the most prevalent (71.4%); the lesser curvature was affected in 28.6% of the cases. The E545K variant of PIK3CA was observed in one EBV^(+) GC case. A combination of clinically significant variants of KRAS and PIK3CA was found in all MSI cases. The BRAF V600E mutation, which is specific to MSI colorectal cancer, was not detected. The EBV^(+) subtype was associated with better prognosis. The five-year survival rates were 100.0 and 54.7% for MSI and EBV^(+) GCs, respectively.

[Clinical portrait of a patient with COVID-19. The experience of a multidisciplinary clinic].

AIM: Evaluation of the clinical characteristics in patients with COVID-19. MATERIALS AND METHODS: The article presents clinical and instrumental data of 1169 patients included in a single-center mixed study. Patients were tested for COVID-19 using polymerase chain reaction, computed tomography (CT), and antibody screening. Clinical history data were collected. RESULTS: In patients with confirmed COVID-19, lung damage and a positive test for antibodies were observed in 75.5 and 45.2% of cases, respectively. The most common symptoms of COVID-19 were: fever (73.2%), weakness, (72.7%) dry cough (62.8%) and shortness of breath (55.4%). Patients with CT-visualized lung lesions were more likely to have clinical symptoms and elevated levels of antibodies. Patients with chronic diseases of the endocrine system, circulatory system, and respiratory system had a more severe course of the disease (CT-14: 91.296.3%) than patients without chronic diseases (CT-14: 85,1%). CONCLUSION: We have compiled a clinical profile of patients with COVID-19 and highlighted the most significant clinical characteristics corresponding to a more severe course of the disease. Our data showed that patients with chronic diseases require a personalized approach and the development of specific criteria for the diagnosis and treatment of COVID-19.

[TNFRSF13B gene mutation in adult patient with common variable immunodeficiency. Case report].

Common variable immunodeficiency (CVID) is one form of the primary immunodeficiencies (PIDs). CVID is characterized by variable clinical manifestations. Genetic alteration is a cause of the disease in many cases. In the current paper we described Patient N of 45 years old, who have been suffering from frequent various infections and therefore attended an immunologist and clinical geneticist. Immunoglobulins (Ig) A, M, and G deficiency was found in the patient. As a result of medical genetic counselling primary immunodeficiency has been suggested as a diagnosis. Further molecular genetic testing using clinical exome sequencing (Next Generation Sequencing method) revealed a likely-pathogenic variant c.204dupA (p.Leu69ThrfsX12, rs72553875) of TNFRSF13B gene in the patient. The gene variant was found in homozygous state. According to the international medical literature and genomic databases TNFRSF13B gene mutations lead to the CVID development and in some patients are characterized by isolated IgA deficiency and in the other group of patients can lead to decrease of IgA, IgM, and IgG. The patient had a family history of cancer and autoimmune inflammatory bowel disease (erosive-ulcerative enterocolitis). Moreover, one sibling of the patient died at the age of 3 weeks from complications of toxoplasmosis infection. The other sibling of 51 years old have been also suffering from recurrent infectious diseases. Thus, the genetic cause of the disease was identified in the proband. It has been shown that homozygosity for variant c.204dupA of TNFRSF13B gene is characterized by the deficiency of all three classes of Ig. Medical genetic counselling and modern molecular genetic methods application is an important step in management of people with signs of immunodeficiency. Such approach helps to make a diagnosis to the patient, to find an exact molecular reason of the condition, to use effective treatment, and to perform preventive measures in patient`s family.