RESUMO
The article discusses results of the structural and functional analysis of molecular genetic abnormalities in various malignant tumors. Investigations have discovered more than 20 new markers for sporadic breast cancer. Several of them formed the test system, allowing the diagnosis with a specificity of 100%. Appearance of TMPRSS2/ERG4 chimeric gene is a frequent tumor-specific event, its expression is correlated with more aggressive forms of prostate cancer, may serve as a molecular marker for tumor cells and androgen assessment of tumor response to hormonal therapy. The effective systems for the early diagnosis of cervix and endometrium cancer were developed as well. Mutations in the VHL, deletions of chromosome 3 and methylation of several genes can predict the course and selection of effective therapy of clear cell kidney cancer, a number of molecular markers were identified for early diagnosis and prognosis of recurrence of bladder cancer. For diagnosis, prognosis and treatment of brain tumors we developed an effective complex system of markers. Protocol of molecular genetics investigation reveals the cause of the disease by more than 90% of patients with retinoblastoma. In order to study abnormal methylation in tumor genomes an innovative technology AFLOAT has been developed that allows to efficiently identify new markers with diagnostic value. Test systems of molecular genetic and epigenetic markers for early diagnosis and prognosis as well as for cancer therapy optimization have shown to be effective, have been approved for use in clinical practice and are being introduced into practical healthcare.
Assuntos
Biomarcadores Tumorais/genética , Diagnóstico Precoce , Testes Genéticos/métodos , Neoplasias , Terapia Combinada , Genoma , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia , PrognósticoRESUMO
To analyze the pattern of molecular damages in urinary bladder cancer (UBC), the authors studied allelic imbalance of chromosome loci 9p21 and 17p13 in 22 patients diagnosed as having multiple primary UBC (2 to 5 foci in each patient). The state of markers has no informative value in 3 (13.6%) cases; in 9 (47.4%) of 19 informative cases, deletion of the same allele was determined in at least one of the loci in question in all tumor nodules, which may point to the monoclonal origin of multiple tumors in these patients. Five (26.3%) of the 19 patients exhibited deletion of the same allele in different tumor nodules, which is suggestive of the active process of clonal evolution and the feasibility of tumor subcloning, which does not preclude the possibility of monoclonal origin. Five (26.3%) of the 19 patients had an imbalance of different alleles in varying nodules, which may show the oligoclonal origin of the tumor nodules concerned. The concordant and discordant patterns of molecular damages are encountered virtually with the same frequency in the tumors of multiple primary UBC, which supports the view that its synchronous tumors can develop both monoclonally through intraluminal dissemination of tumor cells and when there are cancerization fields that determine the occurrence of oligoclonal tumors.
Assuntos
Células Clonais/patologia , Perda de Heterozigosidade , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Alelos , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 17/metabolismo , Cromossomos Humanos Par 9/genética , Cromossomos Humanos Par 9/metabolismo , Feminino , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/metabolismoRESUMO
We have investigated deletions of 3p14, 9p21, 9q34, 17p13 (TP53) loci, activating FGFR3 mutations in exon 9 and aberrant methylation of RASSF1, RARbeta, P16, P14, CDH1 genes with the aim of the molecular pathogenesis pathways analysis of bladder cancer. FGFR3 activating mutations and 9p21 deletions were observed significantly more frequent in the group of non-invasive bladder cancer pTa than in minimally-invasive cancers pT1 (p = 0.004 and 0.006 respectively). It was shown that groups of superficial and invasive bladder cancer are significantly differing in the frequency of 17p13 (p = 0.006) and 9q34 (p = 0.04) deletions and in aberrant methylation of the gene P16 (p = 0.02). We have revealed some differing molecular-genetic alterations in groups of superficial and invasive bladder cancers. Therefore we suppose that these two types of bladder cancer might have different pathways of development.
Assuntos
Biomarcadores Tumorais/genética , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 3/genética , Cromossomos Humanos Par 9/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Linhagem Celular Tumoral , Deleção Cromossômica , Metilação de DNA/genética , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Invasividade Neoplásica , Metástase Neoplásica , Ativação TranscricionalRESUMO
We have examined the existence of intratumoral genetic heterogeneity for LOH on chromosomes 9p21 (p16, p15, p19), 13p14 (RB1), 10q23 (PTEN), 17p (TP53), microsatellite instability and K-RAS point mutations on four different segments of sporadic colorectal cancers. The intratumoral genetic heterogenity was detected in 9/11 (81%) colorectal adenocarcinomas and morphologically validated. These results show that colorectal cancer is highly heterogeneous for these molecular markers. Furthermore, the analysis has shown the order (succession) of the appearance of these molecular anomalies during tumorigenesis on sporadic CRC, and supposed, that K-RAS point mutations, and anomalies of p16-RB1-cyclin D pathway could occur before LOH on 10q23 (PTEN) and microsatellite instability during tumor progression.
