PCR-based detection of EGFR, ALK, KRAS and BRAF mutations in Russian patients with lung adenocarcinoma: a single-center experience.

In contrast to other countries with predominantly white populations, Russian smoking-related lung cancers (LC) are mainly squamous cell carcinomas and approximately half lung adenocarcinomas (AdCa) are not related to tobacco consumption. Given that smoking significantly influences the probability of presence of actionable mutations in LC, one would expect that Russian lung AdCa patients would differ from other white populations in distribution of EGFR, ALK, KRAS and BRAF mutations. Herein, 2,336 consecutive lung AdCa cases, including 1,203 patients with known smoking status, were subjected to sequential testing for the above mutations. One quarter of lung AdCa patients carried either EGFR or ALK mutation with combined prevalence of 42% in those who had never smoked but only 8% in smokers. There was only a moderate difference in KRAS mutation frequency between ever- and never-smokers in EGFR/ALK-negative cases (31% vs. 23%), and this was mainly attributed to increased prevalence of G12C substitution in the former group. The occurrence of BRAF V600E mutation was 1.7% and 4% in EGFR/ALK/KRAS mutation-negative ever- and never-smokers, respectively. ALK testing of 470 EGFR-mutated tumors revealed only 1 (0.2%) instance of translocation. Similarly, KRAS testing identified 1 (1.25%) mutation in 80 EGFR-mutated AdCa and none in 48 ALK-rearranged AdCa. Therefore, concurrent actionable mutations in lung adenocarcinoma are exceptionally rare and sequential gene testing can be regarded as a reliable option.

Spectrum of APC and MUTYH germ-line mutations in Russian patients with colorectal malignancies.

Distribution of cancer-predisposing mutations demonstrates significant interethnic variations. This study aimed to evaluate patterns of APC and MUTYH germ-line mutations in Russian patients with colorectal malignancies. APC gene defects were identified in 26/38 (68%) subjects with colon polyposis; 8/26 (31%) APC mutations were associated with 2 known mutational hotspots (p.E1309Dfs*4 [n = 5] and p.Q1062fs* [n = 3]), while 6/26 (23%) mutations were novel (p.K73Nfs*6, p.S254Hfs*12, p.S1072Kfs*9, p.E1547Kfs*11, p.L1564X and p.C1263Wfs*22). Biallelic mutations in MUTYH gene were detected in 3/12 (25%) remaining subjects with polyposis and in 6/90 (6.7%) patients with colorectal cancer (CRC) carrying KRAS p.G12C substitution, but not in 231 early-onset CRC cases negative for KRAS p.G12C allele. In addition to known European founder alleles p.Y179C and p.G396D, this study revealed a recurrent character of MUTYH p.R245H germ-line mutation. Besides that, 3 novel pathogenic MUTYH alleles (p.L111P, p.R245S and p.Q293X) were found. Targeted next-generation sequencing of 7 APC/MUTYH mutation-negative DNA samples identified novel potentially pathogenic POLD1 variant (p.L460R) in 1 patient and known low-penetrant cancer-associated allele CHEK2 p.I157T in 3 patients. The analysis of 1120 healthy subjects revealed 15 heterozygous carriers of recurrent MUTYH mutations, thus the expected incidence of MUTYH-associated polyposis in Russia is likely to be 1:23 000.

[Post of atmospheric air control for the presence of pathogenic biological agents and its significance in the system of biological threat counteraction].

Contemporary experience of organization of atmospheric air monitoring for the presence of pathogenic biological agents (PBA) is generalized in the article. Proposals for the use of posts of atmospheric air control during mass events are presented. Issues of equipping the instrument base for air sampling and PBA detection are examined.

[Operation preparedness of specialized anti-epidemic brigades during mass events].

Operation experience of specialized anti-epidemic brigades (SAEB) for the support of sanitary-epidemiologic welfare during various emergencies is presented. The order of functioning and SAEB objectives during mass events is examined. Analysis of exercise of Stavropol Institute of Plague Control SAEB was carried out, proposals for augmentation of SAEB equipment table by instruments and reagents for indication and genotyping of pathogen strains are examined.

[The duration of preservation of plague pathogen strains with a different plasmid kit from a Central Caucasian high-altitude natural focus in the organism of citellophilus tesquorum fleas and the possibility of their transmission to laboratory animals].

Two plasmid variants of the main subspecies of the plague microbe circulate in a Central Caucasian high-altitude natural focus of plague. The strains of one plasmid variant fully correspond to the main subspecies of the plague pathogen in their characteristics. Those of the other are auxotrophic for proline, weakly virulent to one or both species of laboratory animals. The mountain subspecies of Citellophilus tesquorum fleas excretes the greatest quantity of plague microbe strains so the investigation of whether unblocked fleas can transmit the plague microbe is of interest.

[Adherence to guidelines on management of acute coronary syndrome in Russian hospitals and outcomes of hospitalization (data from the RECORD-2 Registry)].

BACKGROUND: Complete following existing guidelines for management of acute coronary syndrome (ACS) is known to be associated with better outcomes. Partly this is explained by lesser adherence to recommendations in high risk patients. Aim of our study was to assess relationship between degree of following current guidelines and in hospital outcomes independently from initial assessment of risk. METHODS: Each key recommendation from guidelines issued between 2008 and 2011 (13 for STE ACS, 12 for NSTE ACS) was given weight of 1. Sum of these units constituted index of guideline adherence (IGA). IGA was retrospectively calculated for 1656 patients included in Russian independent ACS registry RECORD-2 (7 hospitals, duration 04.2009 to 04.2011). The patients were divided into 2 groups according to quartiles of IGA distribution: 1) low adherence group (quartiles I-II); 2) high adherence group (quartiles III-IV). RESULTS: In low adherence compared with high adherence group there were significantly more patients more or equal 65 years (=0.0007), with chronic heart failure [CHF] (<0.0001), previous stroke (<0.0001), atrial fibrillation [AF] (=0.0002), Killip class more or equal II (=0.0065), high risk of death by GRACE score (=0.035). Inhospital mortality was 9.3 and 2.4% in low and high adherence group, respectively (p<0.0001). The following independent predictors of inhospital death were identified: IGA quartiles I-II (odds ratio [OR] 4.0; 95% confidence interval [CI] 2.3-7.1; <0.0001), high GRACE score (OR 3.3; 95% CI 1.8-6.0; <0.0001), admission systolic BP less or equal 100 mm Hg (OR 3.1; 95% CI 1.8-5.4; <0.0001), admission serum glucose more or equal 8 mmol/l (OR 2.9; 95% CI 1.8-4.7; <0.0001), age more or equal 65 years (OR 2.3; 95% CI 1.3-4.0; =0.005), ST elevation more or equal 1 mm on first ECG (OR 1.7; 95% CI 1.1-2.5; =0.013). From groups with low and high adherence to guidelines we selected pairs of patients (n=588) with similar (or close) age, type of ACS, GRACE score, Killip class, presence of other important risk factors (CHF, AF, previous stroke), and formed 2 equal subgroups without significant differences in important demographic, anamnestic, clinical and laboratory data. Hospital mortality was 7.8 and 2.7% in low and high adherence subgroup, respectively (p<0.0001). CONCLUSIONS: In RECORD-2 ACS registry low adherence to guidelines was more frequent among high risk patients and was independent predictor of inhospital death. Association between degree of guidelines adherence and outcomes persisted after equalizing groups by some factors of risk of mortality.

[Age-related and clinical-pathogenetic features of colorectal cancer associated with status of K-ras gene].

Activating mutation in K-ras gene is a key event in the pathogenesis of colon carcinoma. This study analyses frequency of this mutation in different age groups of colorectal cancer patients residing in North-Western Russia, and examines its relationship with essential clinical characteristics of tumor disease.

[An estimation of morphofunctional state of the animals of the first generation from parents long time exposed in hazardous area of Chernobyl NPS].

The morphofunctional state offspring of rats first generation in age 3 and 6 monthes from long time exposed males and females in hazardous area of Chernobyl NPS was studied (registration point Masany). At experimental animals the damages in blood, in sex systems, in heredetic apparatus, in morrow cells and in blood lymphocytes were shown, that testify about the effects of low-intensive long-term radiation on organism. Obtained data indicate remote consequences of radiation-ecological factors of environmental surroundings at posterity animal of generation F1 breeding in zone of enhanced radioactive contamination.

[Allelic distribution of the CYP1A1 in lung cancer patients, middle-aged tissue donors and in elderly people without cancer]. / Raspredelenie allelei gena CYP1A1 u bol'nykh rakom lëgkogo, donorov srednego vozrasta i pozhilykh liudei bez onkologicheskoi patologii.

The genetic polymorphism of metabolizers of tobacco smoke carcinogens can influence individual susceptibility to lung cancer. The study was concerned with the Mspl-polymorphism of the CYP1A1 gene responsible for encoding aryl hydrocarbon hydroxylase. It also plays a role in the activation of polycyclic aromatic hydrocarbons (PAH). The CYP1A1 alleles and genotype distribution in 146 lung cancer patients was compared with that in 230 healthy donors. Another control group consisted of 259 "cancer-resistant" subjects, i.e. tumor-free smokers and non-smokers aged 75 and more. The CYP1A1 allele incidence (19%) in patients with squamous lung cancer was significantly higher than in the control cohorts (11%) which is consistent with the leading role of PAH in the etiology of this pathology.

L-MYC and GSTM1 polymorphisms are associated with unfavourable clinical parameters of gliomas.

L-MYC and GSTM1 genotypes were analysed in glioma patients (GP) and healthy donors (HD). None of these genes appeared to influence the risk of this disease, however both polymorphisms correlated with unfavourable clinical parameters of gliomas. In particular, S allele of the L-MYC was overrepresented in the relapsed patients (P < 0.05), and GSTM1-null genotype was associated with the advanced tumour grade (P < 0.05). Patients, but not donors, demonstrated frequent combination of SS L-MYC homozygosity with GSTM1(-) variant (P < 0.01 ), as well as a correlation between LL L-MYC homozygosity and GSTM1 (+) genotype (P < 0.05).

[L-myc and GSTM1 polymorphism in cerebral glioma]. / Polimorfism genov L-myc i GSTM1 u bol'nykh gliomami golovnogo mozga.

L-MYC and GSTMI polymorphisms were studied in glioma patients. L-MYC allele frequency in patients (L: 61/114 (54%); S: 53/114 (46%)) and controls (L: 108/204 (53%); S: 96/204 (47%)) was identical. S allele was associated with certain unfavourable clinical features of the disease. In particular, its frequency was 26/42 (62%) in relapse vs. 26/68 (38%) in relapse-free disease (p < 0.05). GSTMI "null" genotype was identified in both patients and healthy donors (48%). GSTMI-deficient genotypes were significantly predominant in patients with grade III-IV gliomas as compared with grade I-II tumors (p < 0.05). Patients, but not donors, frequently revealed a combination of SS L-MYC homozygosity and GSTMI (-) variant (p < 0.01) as well as an association of LL L0-MYC homozygosity and GSTMI (+) genotype (p < 0.05).

[Correlation between int-2 oncogene amplification and increased tumor size in breast cancer]. / Assotsiatsiia amplifikatsii onkogena int-2 s uvelichennym razmerom opukholi pri rake molochnoi zhelezy.

Amplification of the int-2 oncogene was observed in 10 out of 78 (13%) samples of DNA isolated from cells of primary breast tumor. A clinico-morphological examination established a correlation between this molecular-genetical anomaly and tumor size: gene amplification was detected in 1 out 34 (3%) cases of breast tumor under 2 cm and in 9 out 44 (20%) tumors measuring 2 cm and more (p < 0.05). Similarly, a kind of correlation was found between gene amplification and low differentiation of breast cancer cells: enhanced copying ability of the oncogene was registered in 2 out 4 (50%) breast tumors with low cell differentiation, 8 out 69 (12%) tumors with medium cell differentiation, while it was not identified in 5 breast carcinomas with high cell differentiation (p < 0,2).