Two hundred and two lung adenocarcinomas were examined for epidermal growth factor receptor (EGFR) mutation: exon 19 deletion and L85R mutation in exon 21. The expression of EGFR, Ki-67, bcl-2, p53 in the lung adenocarcinomas was studied in relation to the type of EGFR mutation. Lung adenocarcinomas harboring the EGFR L858R mutation in exon 21 have a less proliferative activity than those with EGFR mutation in exon 19 and in those without EGFR mutation. The p53 protein expression was higher in a group of adenocarcinomas having the EGFR L858R mutation than in that of adenocarcinomas with EGFR mutation in exon 19. There was no bcl-2 expression in adenocarcinomas showing the EGFR mutation.

Earlier in some small cell lung (SCLC) and non-small cell lung carcinoma (NSCLC) cell lines, methylation of CpG-island was found in the SEMA3B region, which belongs to the first intron according to the NCBI data base (Build 36). The aim of this work was to study methylation of two SEMA3B CpG-islands: promoter and intronic in clear cell renal cell carcinoma (RCC). Using methyl specific PCR and bisulfite sequencing, it was shown for the first time that promoter CpG-island was methylated in RCC with high frequency 56% (34/61), and intronic CpG-island - with somewhat lower frequency 35% (17/48). Significant reverse correlation was estimated between mRNA level decrease and methylation of promoter CpG-island in RCC for the first time (P < or = 0.05 by Fisher's exact test), no correlation was determined for intronic CpG-island. This result suggested that methylation of promoter CpG-island contributed into inactivation of SEMA3B gene-suppressor in RCC.

The level of ferritin in serum is known to be increased frequently in most human cancers. Ferritin consists of the heavy and light chains, encoded by FTL and FTH genes. The analysis of the EST database showed that the level of FTL and FTH mRNA is decreased in lung squamous cell carcinomas as compared to the normal tissues, no change in the mRNA level was observed in clear cell renal cell carcinoma. Using real-time PCR we estimated the mRNA level of these genes in primary tumors. It was shown significant and frequent decrease of FTL and FTH mRNA level in lung squamous cell carcinoma: on the average by 11 and 9 times in 83% (33/40) and 73% (11/15) of cases, respectively. In clear cell renal cell carcinoma the changes were not so marked both with respect to the level of decrease (on the average 6 and 3 times) and to its frequency (58 and 27%). In the present work it has been shown for the first time that the FTL mRNA is frequently down-regulated even at the early stages of lung squamous cell carcinoma in all studied samples. This fact permits to consider this gene as potential oncomarker of early diagnosis. The FTL mRNA content may be quantified by non-concurrent hybridization on expression DNA microarrays. The possible causes of a serum ferritin increase in lung cancer and renal cancer are discussed.

Analysis of genetic predisposition to cancer can provide valuable information for early cancer detection or even prevention. Insertion 5382insC in BRCA1 gene is the most frequent mutation among those associated with high risk of breast cancer in women of East European origin. The method of 5382insC detection using fluorescent labeled allele specific oligonucleotides in Duplex Scorpion format has been developed. The method can be used in real-time PCR conditions as well as in conditions of end-point fluorescence measurement followed regular PCR. The adequacy of the method was demonstrated in the study of 5382insC mutation frequency in breast cancer patients. 564 samples of genomic DNA from breast cancer patients were genotyped. Eleven patients (1.95%) were found to be heterozygous for BRCA1 5382insC mutation. 5382insC allele frequency in breast cancer patients group was 0.0098. The method can be used as in clinical practice to determine individuals of a high risk of breast cancer, as in wide-scale population studies.

To estimate the extent of FLT3 and NPM1 gene mutations and the impact of mutations of FLT3-ITD on the survival of patients with acute myeloid leukemias (AML).

To discuss the specific features of the cytogenetics and clinical manifestations of acute lymphoblastic leukemias (ALL) with balanced and unbalanced translocations (1;19)(q23; p13).

Our study is concerned with comparative analysis of diethylnitrosamine (DENA)-induced carcinogenesis in PARP-1 knock-out female mice PARP-1(-/-) and wild type animals PARP-1(+/+). No difference was recorded in relation to total tumor incidence (88 and 95%, respectively): cardia (87 and 84%, respectively), liver (80 and 66%, respectively). However, experimental animals PARP-1(-/-) tended to reveal incidence of cardia tumors with invasion as deep as the serosa higher than in PARP-1(+/+) mice (100 and 81%, respectively) and metastases to the liver and lung--27 and 7%, respectively. Relative incidence of angiosarcoma and holangiocarcinoma among liver tumors from PARP-1(-/-) mice was higher than that in wild type mice. Hence DENA induced the most aggressive tumors in PARP-1(-/-) knockout mice more often than in PARP-1(+/+) ones. Our results confirm the significance of the role of DNA repair in carcinogenesis.

The authors observed 149 patients with nodal goiter and 39 patients with thyroid cancer for thyroid cancer risk factors. Frequency of thyroid cancer, malignancies and thyroid gland diseases was studied in the families of the observed patients. BRAF T1796A gene mutation was identified in 50 tissue samples of thyroid cancer of the patients. It has been shown, presence in relatives thyroid cancer and malignant new growths is thyroid cancer risk factor. BRAF T1796A mutation was identified in 27% of papillary thyroid cancer samples and its identification may be used to determine this risk factor of the development of papillary thyroid cancer clinical form.

Disorders of apoptosis regulation leading to development oftumours associated with expression of one of the main links in the regulation of programmed death of cells (proteins of the Bcl-2 family) were studied.

The regulatory physiological system of a unitary organism, i.e. the organism reproducing only by sexual way, includes along with others the three following mechanisms guaranteeing reliability of the life interruption: 1) senescence; 2) cancer; 3) disintegration in the organism under influence of the factors which action exceeds adaptive abilities of the organism. The three mechanisms are inherited from modular, i.e. reproduced not only by sexual but by asexual way, ancestors, in which organisms the destructive processes were reversible. The conversion of the mechanisms of reversible disintegration into mechanisms of irreversible disintegration is the consequence of progressive evolution.

The problem of the relationships between the macro- and microorganism in Helicobacter pylori infection is discussed in the context of the genetic regulation of inflammation. The leading role of host genetic polymorphism in maintaining an inflammatory response in the absence of the infectious organism is demonstrated, by using previous Helicobacter gastritis as an example. The combinations of polymorphisms of two genes IL-1beta-511T/IL-1RN . 2 and IL-1beta-31T/IL-1RN . 2, which provides an inflammation phenotype associated with the risk of impaired cell renewal and gastric mucosal atrophy, have been identified. The promising use of the phenotype of chronic atrophic gastritis in the present classifications as a prognostic category of gastric cancer is assessed.

Introduction of molecular biological studies into oncomorphology has made investigators reconsider many fundamental notions of the histogenesis, morphogenesis, and microscopic structure of human neoplasms. Tumor cell differentiation is a more dynamic process, a less fixed concept; hence it is necessary to do away with the rigid frameworks of cancer nosological entities and with a number of postulates on tumor histogenesis, including the rudiments of blastemic tissue changed during embryogenesis. The morphogenesis of a tumor has proven to be frequently determined by the variants of the specific translocations that may, in addition to its miscroscopic structure, affect a great variety of the clinical manifestations of disease. The molecular portrait of a tumor, the result of gene expression peculiarities can substitute for traditional cancer nosological entities although new classifications should be based on advances in oncomorphology.

The putative causative relationship between mutator nature of carcinogenesis and positive results of empirical application of supermutagens for anticancer therapy is discussed. Part 1 of the review is devoted to the substantiation of the mutator theory of carcinogenesis. Part 2 provides an explanation of positive results of empirical application of supermutagens for anticancer therapy in the framework of this theory.

Preliminary results of cytogenetic monitoring acute myeloid leukosis (AML) in children are presented. Repeated chromosomal analyses were accomplished in 23 patients that presented with cell clones showing various karyotype abnormalities prior to the onset of therapy. All the patients were treated following identical protocols. Complete hematological remission was achieved in 20 cases. The majority of patients did not have cells with chromosomal abnormalities changes after a 2-4 month follow up. Anomalous metaphases persisted in 6 patients although their occurrence decreased. Five of them poorly responded to therapy whereas simultaneous achievement of morphological and cytogenetic remission ensured more beneficial outcome of the treatment. Results of the study agree with recent reports of delayed reversion to normal karyotype under effect of AML therapy that as a rule predicts an unfavourable prognosis Repeated analysis during stable hematological remission did not reveal cells with karyotype abnormalities in bone marrow with the exception of a single patient who had marrow cells with chromosomal translocation (16:16) up to the 8th month of complete hematological remission. This patient remains under observation (duration of remission is now 15 months). It was shown that the relative amount of cells with abnormal karyotype in bone marrow frequently exceeds that of blast cells (usually before the onset of therapy and sometimes in the beginning of morphological remission). During stable remission, such an excess is an antecedent of relapse. It is concluded that cytogenetic analysis for monitoring AML extends the possibility of detecting leukemia cells.

Colon cancer is one of the leading causes of cancer deaths in developed countries due to the absence of tumor specific markers for early diagnosis of the disease, providing adequate sensitivity. Search for diagnostic markers of various types of cancer by proteomic approaches has been limited by large differences in protein centration. We used preliminary extraction of major cellular proteins by 0.2 M sodium chloride in presence of nonionic detergent NP-40 in order to raise the sensitivity of the 2D PAGE detection of low-abundant soluble proteins, some of which may penetrate in blood circulation during carcinogenesis. Application of this procedure prior to 2D comparative analysis of proteomes of normal tissues and matched colon cancer specimens led to selection of ten proteins, which are frequently overexpressed in colon adenocarcinomas. Mass-spectrometric identification of selected proteins led to discovery of two novel protein markers of colon tumors--TAF9 and CISH. Low level of CISH expression in various tissues suggests that it is a novel prospective marker for diagnosis of colon cancer.

Earlier we have shown high frequency of loss of heterozygosity of microsatellite marker D6S273 within HLA III class region in DNA samples from cervical intraepithelial neoplasias and cervical cancer. According to publications three genes were identified in this region. For detection of D6S273 position we used in silico analysis of mRNA sequences deposited in GenBank (NCBI) and investigated LY6G6D gene expression in tumor cell lines. LY6G6D gene exon borders were analyzed with 5'- or 3'-rapid amplification of cDNA ends. We have found that LY6G6D gene consists of 9 exons and includes two earlier identified genes G6D and G6F. Microsatellite D6S273 is located in the last 8 intron of LY6G6D gene. The third gene LY6G6E consisting of four exons is located in 6 intron of LY6G6D gene in the opposite orientation. We suggest that LY6G6D gene is coding three main mRNA transcripts in the same open reading frame but differ in exon composition: MEGT1 consists of 1-4, 8, 9 exons, G6F consists of 1-6 exons and G6D consists of 7-9 exons of LY6G6D gene. High homology with immunoglobulin superfamily within 20-120 aminoacids of MEGT1 and G6F proteins is shown by in silico translation of their mRNAs.

To analyse clinical implications of chromosome 8 trisomy in Ph-negative cells of the bone marrow in patients with chronic myeloid leukemia (CML) treated with inhibitors of tyrosinkinases (ITK).

High prevalence of colorectal cancer makes it a most serious socio-medical problem. Hence, the necessity of overall screening for prodromal changes and malignant neoplasms at the early stages of the disease. Despite a variety of efficacious instrumental diagnostic tools, the development of non-invasive screening techniques based on recent progress in understanding molecular mechanisms of carcinogenesis remains a highly topical issue. A pathogenetic model of colorectal cancer and pathophysiological basis of screening for colonic neoplasms are considered with the emphasis on the detection of tumour cells in faeces and their DNA carrying mutations in suppressor genes and oncogenes. Results of the studies with the use of one or several DNA oncomarkers are analysed in the context of their value for the diagnosis of colorectal neoplasms. High sensitivity and specificity of these methods make them very promising for application to the screening for colorectal cancer.