Carriers of GSTTI gene deletion were found to be more subjected to a risk of emerging non-small-cell lung cancer (NSLC) than those of normal GSTT1(+) genotype. Study on the relation between GST gene polymorphism and cytogenetic indices in lung cancer patients has shown a significant excess of the group average level in cells with micronuclei in NSLC patients with GSTTI(-). The frequency of cells with micronuclei was higher in smoking patients with a mutant genotype than in smoking carriers of the GSTT1(+) genotype.

Prognostic significance of additional karyotype abnormalities was studied in 73 children with t(8,21) acute myeloid leukemia (AML). Additional chromosomal aberrations were documented in 61 cases (83.6%). The loss of sex chromosomes and/or deletion of the long arm of chromosome 9 (9q-) were predominant abnormalities, in agreement with the literature data. Other additional abnormalities detected in 14 cases were tentatively designated as "atypical". Comparison of pretreatment cytogenetic data and those obtained during relapses revealed the previously unknown rise in the frequency of atypical abnormalities in AML relapses (to 63.6% vs 19.2% at the first presentation, p < 0.005). It is supposed that atypical additional abnormalities reflect relatively late stages of leukemia, and their presence before therapy predicts poor prognosis. In fact, general, relapse-free, and uneventful survival rates in patients with atypical abnormalities were significantly lower that in the remaining patients with t(8;21) AML. Poor survival was associated not only with early relapses but also with high mortality from fatal infections soon after onset of treatment. The incidence of fatal infections in this group was significantly higher than in patients without atypical abnormalities (p = 0.027). Atypical additional abnormalities are rather variable and each variant should to be specifically characterized to estimate its prognostic significance. Our results need to be verified in a larger-scale multicentre study.

The cycle of researches of the influence of an exposion of mice of line Af in the conditions of the zone of Chernobyl disaster on spontaneous and chemically induced mutability, lung tumour (adenomas), morphological and functional condition of alveolar macrophages, and also genetic effects in natural populations wild rodents is executed. The increase in polychromatic frequency in mouse bone marrow, adenomas in lungs, and change of sensitivity of an organism to action mutagen and transgenerational transfer of genetic damages is shown.

One of the systems that regulate tissue homeostatis is gap junction intercellular communications (GJIC). Inhibition of GJIC is widely used in experiments as a characteristic of tumor promotion. It is accepted that the down-regulation of GJIC is tightly related with the tumor-promoting properties of carcinogens. In this study, the effect of some carcinogenic polycyclic aromatic hydrocarbons on GJIC in cell cultures of hepatoma 27 lacking cytochrome P450 and Ah receptor was investigated. It was shown that inter 6 compounds studied only benzo/a/pyren and 3-methylcholanthrene were able to inhibit GJIC. We have concluded that an unknown factor is present in hepatoma cells and its interaction with some polycyclic aromatic hydrocarbons results in GJIC inhibition. The investigation of mutual effect of benzo/a/pyrene and non carcinogenic benzo/e/pyrene with similar structure has shown that GJIC inhibition by benzo/a/pyrene is at least double stepped.

The purpose of this study was to investigate informativety and clinical significance of most frequent somatic alterations in K-ras, TP53, CDKN2A, MADH4 and more uncommon mutations in BRCA1, BRCA2, CHEK2 genes, which arise on preinvasive stage in sporadic pancreatic adenocarcinomas (PA), in Russian patients. We examined surgically resected and manually microdissected primary PA tissue samples and samples of normal pancreatic tissue for 37 individuals. K-ras mutations in codon 12 were found in 24 tumors (0.65) and none of normal tissue samples. No mutations were detected in BRCA1(185delAG, 300T > G, 4153delA, 4158A > G,5382insC), BRCA2 (695insT, 6174delT) and CHEK2 (1100delC) genes. Informativety for allelic loss of three tumor suppressor genes studied had not statistically significant differences: 60% - for TP53 (GDB186817) and CDKN2A (D9S974 + D9S162); and 65.7% - for MADH4 (D18S363 + D18S474) (t = 0.48). Maximal frequency of loss of heterozygosity (LOH) was observed for CDKN2A - 0.95. For TP53 and MADH4 it was 0.62 and 0.70 respectively. The tumors included 80% cases showing LOH on different chromosomal loci. The combination of K-ras mutations (c.12) and LOH at 9p, 17p and 18q resulted in a high informativety of selected molecular markers: 85.7%. Instability of microsatellites was found only in 9% of PA.

Polyfunctional protein PML contributes significantly in vital activity of cell. 11 isoforms of PML differ from one another by C-terminal domain. In spite of intensive research into the protein, the role of the isoforms in cellular processes remains obscure. In addition, the literature contains various names of the isoforms. The goal of this work was to review the structure of the PML gene, variants of alternative splicing of mPNA, and domain organization of corresponding protein forms. The PML isoforms were classified and functional specificity of each PML isoform was characterized: contribution to gene transcription, contribution to cell apoptosis, cell growth, immune response, formation of nuclear bodies.

Polymorphisms in genes involved in steroidogenesis as well as sensitivity to insulin as potential cancer risk factors have received constantly-growing attention over this decade. The peculiarities of endocrine and metabolic features of cancer identified earlier in BRCA1 mutation carriers prompted an investigation of the frequency of polymorphisms in the genes of IRS-1 and enzymes of estrogen biosynthesis and metabolism, such as aromatase (CYP19), estrogen 4-hydroxylase and catechol-O-methyl transferase (COMT) in 12 BRCA1 mutation carriers and in 22 non-carriers. The results were compared with the earlier data from the patients with the same diagnosis (n = 110 and n = 295, respectively) but untested for BRCA1 mutation. BRCA1 mutation carriers tended to show increasing fractions of heterozygotes for AG (COMT Vall58Met p = 0.24) and active allele A6 featuring 11 TTTA repeats in the 4-th introne [corrected] of CYP19 gene (p 0.09). [corrected] The frequency of co-occurring CC (CYP1B1) Arg48Gly), AG (COMT Vall58Met ) and A6 (CYP19) in BRCA1 mutation carriers (5 out of 12, 41.6% ) was significantly higher than that in non-carriers (2 out of 22, 9.1% ) (p = 0.03). Immunohistochemical assay showed aromatase expression levels to be the highest among cases of BRCA1 mutation and A6 (CYP19) while CYP1B1 expression was the highest in those of combination of BRCA1 mutation and low-activity AA genotype (COMT Vall58Mer). Our results warrant further large-scale cooperative studies of the problem.

The paper reviews the data available in the literature on a role of the tumor suppressor ARF in oncogenesis and considers the structure of a gene encoding ARF protein. The p53-dependent and p-53-independent functions of this protein are under many studies. There is evidence for the implication of ARF in angiogenesis. There is more and more information on the role of ARF in the regulation of a cell cycle, apoptosis, and autophagy. The importance of this tumor suppressor in the mechanisms of carcinogenesis is beyond question as the inactivation of ARF suppressor activity leads to the rapid growth of neoplasia. However, the exact mechanisms of ARF action yet remain unclear and require further studies by different specialists at both the molecular genetic and other levels of investigation.

Previous studies demonstrated that patients with oligodendroglial tumors (OT) have longer overall and recurrence free survival than patients with other glial tumors of the same grade. Recent investigations showed high influence of genetic alterations on patients' outcome: overall and recurrence free survival increased in the case of presence 1p19q deletion and decreased in the presence of 9p or 10q deletion and/or EGFR amplification. In the series of 241 cases (107 male, 134 female patients, median age -- 38 years, (16-73)) we analyzed the impact of histology, tumor grade and genetic alterations on time to tumor progression (TTP). All patients underwent surgical resection of tumor or biopsy from 2000 to 2005. 70 patterns (oligodendroglioma (O) -- 13 cases, oligoastrocytoma (OA) -- 13, anaplastic oligodendroglioma (AO) -- 30, anaplastic oligoastrocytoma (AOA) -- 14) were assessed by fluorescent in situ hybridization. Median follow up was 24 months. The type of tumor (pure or mixed) didn't influence survival. TTP of patients with grade II and grade III tumors was 37.7 and 48.2 months, respectively (p = 0.035). Deletion 1p19q was noted in 34 (49%) cases. In pure O codeletion 1p19q was detected more frequently (in O -- 75%, in AO -- 56%) than in mixed tumors (in OA -- 31%, in AOA -- 35%). Deletions 9p, 10q and EGFR amplification were noted in 5, 6 and 4 cases, respectively. None of the tumors with 1pl9q deletion had other genetic alterations. Thus, we generated three prognostic groups: A -- deletion 1p19q; B -- balanced chromosomal profile; C -- deletion 9p. Median TTP in groups A, B and C was 46.6, 25.3 and 6.4 months, respectively (p < 0.001). The percentage of OT with 1p19q codeletion was lower than in previous studies. Pure O more frequently had 1p19q deletion than mixed tumors. Genetic alterations predict outcome stronger than histological criteria.

To elucidate the role of some viral and cellular proteins in the occurrence and development of HERV-K-associated germ-cell tumors (GCT), reverse-transcription polymerase chain reaction using specific primers has been employed to study the transcription of the protein Rec HERV-K and the possible interaction of the protein Rec(cORF), that has transforming properties, and the cellular protein PLZF, that is a negative regulator of cell division, in human GCT tissues, in the testicular parenchyma adjacent to a tumor, and in the normal testicular tissues. It was shown that there was expression of Rec(cORF) of mRNA, rather than cellular PLZF in all malignant GCT tissues, this led to the conclusion that no interaction occured between the Rec HERV-K and PLZF proteins in the GCT cells. At the same time co-expression of Rec and PLZF protein was first revealed at the level of transcription in the testicular parenchyma adjacent to a tumor that exhibited carcinoma in situ cells. By taking into account that the protein Rec HERV-K has transforming activity and it is presumed to be Implicated in the development of GCT, the authors discuss a possible role in the Rec HERV-K/HTDV and cellular PLZF interaction in the pathogenesis of GST at the early stages of its genesis.

Breast cancer in germline BRCA1 mutation carriers features a peculiar endocrine and metabolic profile which is yet to be studied properly in clinical settings. We used a novel immunohistochemical method to compare expression levels of aromatase, estrogen 4-hydroxylase (CYP1B1) and fatty acid synthetase in breast cancer tissues from 12 BRCA1 mutation carriers and 22 non-carriers. Rates of aromatase in carriers were significantly higher than in control (p=0.04) to match the data obtained earlier in cell lines employed in down-regulation of the wild BRCA1 gene. These findings make a case for use of aromatase inhibitors in such patients. No differences in CYP1B1 and fatty acid synthetase expression levels were found between the mutation and the wild BRCA1 gene groups. Further search is warranted for manifestations of excess genotoxic effects of estrogens and enhanced lipogenesis in BRCA1 mutation carriers.

Under analysis were results of genetic investigations of 105 patients with thyroid cancer (TC) treated from 2004 through 2007 in the St. Petersburg City Center of surgery and oncology of the endocrine system organs. The patients' age was from 17 to 80 years (mean age 51.6 +/- 1.9 years). The influence of functional variants of matrix metalloproteinase genes in TC was determined. A reliable correlation was noted between certain gene markers and TC patients' age. An association was revealed between matrix metalloproteinase-3 5A (more active allele) and size of the tumor. A reliably decreased frequency of hyperactive genotype MMP-1 2G was detected in a group of women with metastatic forms of papillary cancer as compared with patients without metastases. It was shown that MMP genes could be a substantial factor of slowing down the rate of malignant growth and invasive properties of cancer of the thyroid gland.

Modern proteomic techniques make it possible to identify numerous changes in protein expression in tumor in comparison to normal tissues. Despite the wide application of proteomics in current studies, identification of proteins with stable concentration differences in normal and cancer cells remains rather difficult. The current study was directed to the search of new potential protein colorectal cancer markers using comparative proteomics of protein extracts obtained from primary tumors and adjacent normal tissues. This widespread neoplasm is characterized by lack of evident symptoms at early stages of cancerogenesis. It is highly important to develop fast and sensitive methods of molecular diagnostics. We studied paired cancerous and normal clinical tissue samples from 11 patients with colorectal adenocarcinomas by comparative 2-D PAGE and MALDI-TOF mass-spectrometry identification. Sixteen proteins with stable differential expression were selected and identified, including 13 overexpressed and 3 downregulated proteins. In summary, we describe the discovery overexpression of GPD1 and RRBP1 proteins and lack of expression for HNRNPH1 and SERPINB6 proteins which are new candidate biomarkers of colon cancer.

New comparative genome hybridization technology on NotI-microarrays is presented (Karolinska Institute International Patent WO02/086163). The method is based on comparative genome hybridization of NotI-probes from tumor and normal genomic DNA with the principle of new DNA NotI-microarrays. Using this method 181 NotI linking loci from human chromosome 3 were analyzed in 200 malignant tumor samples from different organs: kidney, lung, breast, ovary, cervical, prostate. Most frequently (more than in 30%) aberrations--deletions, methylation,--were identified in NotI-sites located in MINT24, BHLHB2, RPL15, RARbeta1, ITGA9, RBSP3, VHL, ZIC4 genes, that suggests they probably are involved in cancer development. Methylation of these genomic loci was confirmed by methylation-specific PCR and bisulfite sequencing. The results demonstrate perspective of using this method to solve some oncogenomic problems.

On the model of transplanted leukemia p-388, cytophotometry has shown that tumors' impact on the body includes two stages: direct affection of the target organ, indirect affection through changes in functional relations with cell populations of other organs due to the impact of transformed cells of the damaged target organ. Moreover, the progress of tumor growth alters functional relations between the organs.

Studies of molecular mechanisms of neoplastic transfromation are being under the thorough investigation, reveal the new genes involved into the tumor development. These genes and their products are potential tumor markers and levels of their expression can be detected using modem assays characterized by high specificity and sensitivity. The review highlights the current status of the molecular diagnostics of gastric cancer, including protein and nucleic acids biomarkers. The genetic and epigenetic changes, which are detected in the malignant and nonmalignant tumor tissue DNA and in the blood plasma DNA from tumor bearing patients, are summarized.

We present the results of cytogenetic monitoring of the districts in Kemerovo region, which differ in standardized indices of cancer incidence. It has been shown that residents of the districts with high incidence of malignancies had higher average frequency of metaphases with chromosomal aberrations than the control group (4.06 +/- 0.12% and 2.76 +/- 0.13%, respectively). This difference is caused primarily by single or paired fragments. The increase in the frequency of aberrant metaphase incidence in the districts with elevated cancer frequency was observed both in the male and female groups as well as both in adults and children.