[Genotyping of BRCA1, BRCA2 and CHEK2 germline mutations in Russian breast cancer patients using diagnostic biochips].

Germline mutations of BRCA1/2 genes cause the predisposition of their carriers to breast or/and ovary cancers (BC or/and OC) during the lifetime. Identification of these mutations is a basis of molecular diagnosis for BC susceptibility. Rapid genotyping technique using microarrays for identification of BRCA1 185delAG, 300T>G, 4153delA, 5382insC mutations and 4158 A>G sequence variant; BRCA2 695insT and 6174delT mutations; 1100delC mutation in CHEK2 gene was applied for 412 randomly collected breast cancer samples from the central region of European area of Russia.

[Molecular genetics study of hereditary predisposition to diffuse gastric cancer in Russian patients].

About 3% of cases of gastric cancer (GC) cases are due to hereditary predisposition. Molecular causes of inherited predisposition to diffuse GC among Russian patients have not been studied. In the present work there was performed the molecular genetics study in 9 probands with signet-ring cell GC.

[Cell-free DNA fragments increase transcription in human mesenchymal stem cells, activate TLR-dependent signal pathway and supress apoptosis].

Human mesenchymal stem cells (MSCs) are now widely adopted in regenerative medicine. However, many questions on the role of different signaling pathways in the regulation of stem cell (SC) functional activity within the organism remain unaswered. In damaged regions the level of cell death increases and DNA fragments from dead cells (cell-free DNA, cfDNA) are accumulated in blood.

[Comparison of different methods of molecular-genetic analysis of somatic mutations in K-ras gene in patients with colorectal cancer].

Two approaches to somatic point mutations in 12 and 13 codones of K-ras gene were analyzed: PCR/SSCP/ACRS/sequencing and allele-specific PCR in the real-life regimen (Russian set "KRAS-7M"). The comparison was carried out on 62 examples of genomic DNA extracted from frozen colon carcinomas, which underwent manual dissection. The results obtained in two attempts were consistent in 95,2% (N=59).

[Localization of point mutations in the coding part of the VHL gene in clear cell renal cancer].

VHL gene is often inactivated in sporadic clear cell renal cancer (CCRC) due to somatic mutations, and it's germline mutations cause hereditary CCRC--von Hippel-Lindau syndrome. Localization of mutations in VHL, identification of new mutations and their influence on CCRC progression and sensitivity to targeted therapy are actual problems in modern oncogenetics. We have provided search and characterization of mutations in 248 primary CCRC using SSCP-analysis and sequencing.

[Detection of KRAS mutations in tumor cells using biochips].

Somatic mutations in the KRAS gene are important markers of some types of tumors, for example, pancreatic cancer, and may be useful in early diagnostics. A biochip has been developed which allows determining most frequent mutations in 12, 13 and 61 codons of the KRAS gene. To increase the sensitivity of the method and to make possible the analysis of minor fractions of tumor cells in clinical samples the method of blocking a wild type sequence PCR amplification by LNA-oligonucleotides has been used.

[Li-Fraumeni syndrome: clinico-molecular diagnostics and medico-genetic counseling].

Li-Fraumeni syndrome (sarcoma family syndrome, OMIM 151623) is a rare clinically and genetically hetergoeneous autosomal dominant disorder characterized by the evolvement and accumulation of soft-tissue osteogenic sarcomas in members of a family, as well as uni- and bilateral breast cancer in young women, brain tumours, adrenocortical cancer, and lymphoproliferative diseases. Germinal mutations of the TP53 gene constitute the etiological genetic basis of Li-Fraumeni syndrome. American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network developed recommendations for genetic testing and observation of carriers of TP53 mutations.

[Bystander effect development in human mesenchymal stem cells after exposure to adaptive dose of X-radiation].

Transposition and mutual approaching of pericentromeric loci 1q12 of homological chromosomes from the nuclear membrane towards the nuclear centre as well as activation of the chromosomal nucleolus-forming regions (NFR) are observed in human mesenchymal stem cells (hMSCs) as an initial stages of the adaptive response (AR) after exposure to low doses of X-radiation (10 cGy). All these reactions are also induced after addition of cultivation medium from irradiated cells to intact bystander-cells and this phenomenon called bystander effect (BE). Recently the same AR and BE induction results were obtained for human G0-lymphocytes.

[The response of human cancer stem cells on low-dose X-ray exposure].

Recently we found that transposition of homologous chromosomes 1q12 loci towards the nuclear centre and activation of the chromosomal nucleolus-forming regions (NFR) are observed in human lymphocytes after exposure to low doses of X-radiation (10 cGy). These cell reactions were studied for human breast cancer stem cell cultures. There are two cell types in cell culture from single donor: with two (type 1) and three (type 2) loci of 1q12.

The International Testicular Cancer Linkage Consortium: a clinicopathologic descriptive analysis of 461 familial malignant testicular germ cell tumor kindred.

Objectives: Familial aggregation of testicular germ cell tumor (TGCT) has been reported, but it is unclear if familial TGCT represents a unique entity with distinct clinicopathologic characteristics. Here we describe a collection of familial TGCT cases from an international consortium, in an effort to elucidate any clinical characteristics that are specific to this population.

Materials And Methods: Families with >or=2 cases of TGCT enrolled at 18 of the sites participating in the International Testicular Cancer Linkage Consortium were included.

Analysis of the DND1 gene in men with sporadic and familial testicular germ cell tumors.

A base substitution in the mouse Dnd1 gene resulting in a truncated Dnd protein has been shown to be responsible for germ cell loss and the development of testicular germ cell tumors (TGCT) in the 129 strain of mice. We investigated the human orthologue of this gene in 263 patients (165 with a family history of TGCT and 98 without) and found a rare heterozygous variant, p. Glu86Ala, in a single case.

[Analysis of BRCA1/2 and CHEK2 mutations in ovarian cancer and primary multiple tumors involving the ovaries. Patients of Russian population using biochips].

Ovarian cancer (OC) is one of the leading cause of cancer death in women. Inherited BRCA1 and BRCA2 mutations strikingly increase OC risk (with lifetime risk estimates ranging at 10-60%). Mutation 1100delC in CHEK2 gene was shown to be associated with breast cancer in women carrying this mutation.

Genome-wide linkage screen for testicular germ cell tumour susceptibility loci.

A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM.

The Y deletion gr/gr and susceptibility to testicular germ cell tumor.

Testicular germ cell tumor (TGCT) is the most common cancer in young men. Despite a considerable familial component to TGCT risk, no genetic change that confers increased risk has been substantiated to date. The human Y chromosome carries a number of genes specifically involved in male germ cell development, and deletion of the AZFc region at Yq11 is the most common known genetic cause of infertility.

[Analysis of polymorphic variants of gene GIPC1 CGG repeats in healthy individuals and in patients with breast cancer and non-small cell lung cancer].

The GIPC1 gene product promotes clustering of some transmembrane receptors, including those involved in carcinogenesis, and protects them against ubiquitin-dependent degradation. The 5' untranslated region of GIPC1 contains a polymorphic trinucleotide CGG repeat, which has not been characterized earlier. In the present study, we have carried out comparative analysis of the allele and genotype frequencies of this repeat in 129 samples of breast cancer (BC), 58 samples of non-small cell lung cancer (NSCLC), and 215 samples of healthy donors.

[Population genetic analysis of the association between the BRCA1 and P53 gene polymorphisms and the risk of sporadic breast cancer].

Polymorphism of two tumor-suppressor genes, BRCA1 and P53, was examined. DNA was extracted from blood leukocytes of the women affected with breast cancer (N = 151) and of the women with no clinical symptoms of tumor diseases (N = 191). Typing of the polymorphic variants was performed using PCR-RFLP method.

Somatic mutations of KIT in familial testicular germ cell tumours.

Somatic mutations of the KIT gene have been reported in mast cell diseases and gastrointestinal stromal tumours. Recently, they have also been found in mediastinal and testicular germ cell tumours (TGCTs), particularly in cases with bilateral disease. We screened the KIT coding sequence (except exon 1) for germline mutations in 240 pedigrees with two or more cases of TGCT.

[Association of polymorphism of genetic markers of CYP19 and CYP17 with sporadic breast cancer].

Polymorphic alleles of CYP17 and CYP19, which are involved in estrogen biosynthesis, were tested for association with breast cancer (BC). Microsatellite (TTTA)n and 3-bp deletion of CYP19 and single-nucleotide polymorphism T27C of CYP17 were analyzed in 123 BC patients and 119 healthy women. Of the six (TTTA)n alleles observed, allele (TTTA)8 proved to be associated with BC (11.

[Abnormal methylation of several tumor suppressor genes in sporadic breast cancer].

Multiplex methylation-sensitive PCR was employed in studying the methylation of CpG islands in the RB1, p16/CDKN2A, p15/CDKN2B, p14/ARF, CDH1, MGMT, HIC1, and N33 promoter regions in breast carcinoma (105 tumors). Methylation was often observed for the two major suppressor genes involved in cell-cycle control through the Cdk-Rb-E2F signaling pathway, RB1 (18/105, 17%) and p16 (59/105, 56%); both genes were methylated in 13 tumors. Methylation involved p15 in two (2%) tumors; CDH1, in 83 (79%) tumors; MGMT, in eight (8%) tumors, and N33, in nine (9%) tumors.

[Analysis of mutations in the RET proto-oncogene in patients with medullary thyroid tumor].

The spectrum of mutations of the RET protooncogene was analyzed in Russian patients with inherited or sporadic medullary thyroid carcinoma (MTC). Four RET exons (11, 13, 15, and 16) were subjected to molecular analysis, and mutations were revealed and identified in 47.4% (9/19) patients with sporadic MTC.

[Hereditary cancer: identification, genetic heterogeneity, medico-genetic consult].

The paper deals with a role of inherited factors responsible for the occurrence of malignant tumors. Inherited types of cancer are shown to occur virtually at its sites and averaged 5-15%. Formalized criteria for identifying inherited cancer diseases and their etiological and genetic heterogeneity are presented.

[Molecular diagnosis of multiple type 2 endocrine neoplasia].

The paper reviews the data on the molecular structure of the protooncogene RET encoding for receptor-type protein kinase, on the mechanism of transformation of the normal protooncogene RET to a dominant transforming oncogene, and on RET mutations detected in patients with the MEN-2 syndrome. Moreover, it presents the authors' own findings. The familial medullary thyroid carcinoma burdened genealogy shows a new point mutation TCG(Ser)-->GCG(Ala) in codon 891, in the exon 15 of the protooncogene RET.