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This study aimed to clarify genetic and epigenetic alterations that occur during lung carcinogenesis and to design perspective sets of newly identified biomarkers. The original method includes chromosome 3 specific NotI-microarrays containing 180 NotI clones associated with genes for hybridization with 40 paired normal/tumor DNA samples of primary lung tumors: 28 squamous cell carcinomas (SCC) and 12 adenocarcinomas (ADC). The NotI-microarray data were confirmed by qPCR and bisulfite sequencing analyses. Forty-four genes showed methylation and/or deletions in more than 15% of non-small cell lung cancer (NSCLC) samples. In general, SCC samples were more frequently methylated/deleted than ADC. Moreover, the SCC alterations were observed already at stage I of tumor development, whereas in ADC many genes showed tumor progression specific methylation/deletions. Among genes frequently methylated/deleted in NSCLC, only a few were already known tumor suppressor genes: RBSP3 (CTDSPL), VHL and THRB. The RPL32, LOC285205, FGD5 and other genes were previously not shown to be involved in lung carcinogenesis. Ten methylated genes, i.e., IQSEC1, RBSP3, ITGA 9, FOXP1, LRRN1, GNAI2, VHL, FGD5, ALDH1L1 and BCL6 were tested for expression by qPCR and were found downregulated in the majority of cases. Three genes (RBSP3, FBLN2 and ITGA9) demonstrated strong cell growth inhibition activity. A comprehensive statistical analysis suggested the set of 19 gene markers, ANKRD28, BHLHE40, CGGBP1, RBSP3, EPHB1, FGD5, FOXP1, GORASP1/TTC21, IQSEC1, ITGA9, LOC285375, LRRC3B, LRRN1, MITF, NKIRAS1/RPL15, TRH, UBE2E2, VHL, WNT7A, to allow early detection, tumor progression, metastases and to discriminate between SCC and ADC with sensitivity and specificity of 80-100%. Show less

The aim of the work was to study the clinical and genetic factors at children with obese that predispose to the development of MS, and the development of algorithm for generating risk of MS. Two comparable age and sex groups of children--148 children with obesity and 46--with normal body weight. We assessed anthropometric indices, blood pressure (BP), lipid profile, carbohydrate metabolism, the level of uric acid. 83 children with obesity were genotyped for polymorphisms: I/D gene ACE, G-75A ApoA1, S19W ApoA5, Sstl ApoC3, E2/E3/E4 ApoE and W/R ADRB3. 98,0% of children had abdominal obesity. In 35,8% was identified high blood pressure. In 47,4% was diagnosed hypo-alpha cholesterolemia and/or hypertriglyceridemia (HTG). In 21,0% of children was identified hyperglycemia. 25,7%were suffered from hyperuricemia. Among the genotyped children 57,0% of homo-and heterozygous carriers of D allele ACE gene had high blood pressure. More than half of the holders of 19W-allele ApoA5 (68,5%),--75A-allele of ApoA1 (56,0%), 52-allele of the gene ApoC3 (53,0%), E4-ApoE gene (85,7%), in the heterozygous state had metabolic TG and/or HDL. In 60,3% of the carriers W/W genotype of ADRB3 gene revealed a combination of hyperglycemia with hyperinsulinemia and/or TG. As a result of, aiming aimed at early detection of the major manifestations of MS clinical and genetic study was revealed stable combination of constitutional, metabolic and molecular-genetic factors. Based on these data was developed algorithm for forming groups at risk of MS and individual tactics to prevent and/or therapy. Show less