RESUMO
Detection of residual tumor cells in the circulation can provide prognostic as well as therapeutic information and help in identifying patients at high risk for developing metastases. Maspin and mammaglobin are two molecules that are specifically associated with breast cancer. We looked for mammaglobin and maspin transcripts in the peripheral blood of patients with breast cancer and evaluated their utility as a marker of the response to therapy. Maspin and mammaglobin transcripts were analyzed in 85 breast-cancer patients by nested RT-PCR, prior to and after treatment. Before therapy, 10 patients were found positive for mammaglobin and 20 patients were positive for maspin. In four patients, both transcripts were detected. Immediately following treatment, only one patient was still positive for mammaglobin while maspin transcripts persisted in three patients. Disease progression was observed mainly in patients in whom maspin transcripts were not detectable. Molecular detection of circulating tumor cells during therapy based on analysis for mammaglobin and maspin transcripts is an easy and practical method that can be applied to follow-up patients. We suggest that detection of mammaglobin mRNA is useful to determine the effect of therapy while maspin transcripts may indicate more aggressive disease.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/terapia , Proteínas de Neoplasias/genética , RNA Mensageiro/sangue , RNA Neoplásico/sangue , Serpinas/genética , Uteroglobina/genética , Adulto , Biomarcadores Tumorais/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Progressão da Doença , Feminino , Humanos , Mamoglobina A , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Prognóstico , Transcrição GênicaRESUMO
It has been reported that the p53Arg homozygous genotype could be a potential genetic risk factor for cancer. In this study we investigated the proportion of p53 codon 72 genotypes in patients with colon cancer and compared to a control population. A region of the p53 gene containing the polymorphic site was amplified by PCR and the genotypes were determined by restriction enzyme digestion. No significant difference was found between genotype frequencies in the study groups. Infection with human papilloma virus was also investigated in the tumor samples. HPV 18 and HPV 33 infection was observed in a considerable number of the tumor samples. Incidence of HPV infection did not show a correlation with the genotypes. Thus the p53 genotypes do not seem to be associated with risk of colon cancer or HPV infection.
Assuntos
Neoplasias do Colo/genética , Neoplasias do Colo/virologia , Genes p53/genética , Papillomaviridae , Infecções Tumorais por Vírus/virologia , Adulto , Eletroforese em Gel de Poliacrilamida , Feminino , Frequência do Gene , Genótipo , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de RiscoRESUMO
To date, BRCA1 and BRCA2 mutations in breast and/or ovarian patients have not been characterized in the Turkish population. We investigated the presence of BRCA mutations in 53 individuals with a personal and family history of breast and/or ovarian cancer, and 52 individuals with a personal history of breast cancer diagnosed below age 50 without additional family history. We have identified 11 mutations (nine BRCA1 and two BRCA2) using combined techniques involving protein truncation test, direct sequencing and heteroduplex analysis. We found eight out of 53 patients (15.1%) with a family history to carry BRCA gene mutations (seven BRCA1 and one BRCA2). Of these, four were found in 43 families presenting only breast cancer histories, and four were found in families presenting ovarian cancer with or without breast cancer. We also demonstrated two BRCA1 and one BRCA2 mutations in three out of 52 (5.8%) early-onset breast cancer cases without additional family history. Three of nine BRCA1 and both BRCA2 mutations detected in this study were not reported previously. These mutations may be specific to the Turkish population. The BRCA1 5382insC mutation, specific to Ashkenazi and Russian populations, was found twice in our study group, representing a possible founder mutation in the Turkish population.
Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/genética , Fatores de Transcrição/genética , Adulto , Proteína BRCA2 , Neoplasias da Mama/etnologia , Análise Mutacional de DNA , DNA de Neoplasias/análise , Feminino , Genética Populacional , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/etnologia , Turquia/etnologiaRESUMO
Telomeres are repeated DNA sequences, positioned at the ends of chromosomes and are essential for the stable maintenance of chromosomes. The telomere length serves as a mitotic clock determining the remaining replicative capacity of the cell. Telomeric sequences are lost during each cell division, leading to a process thought to contribute to senescence and cell death. The enzyme telomerase adds 5'-TTAGGG-3' repeats to the mammalian telomeres and maintains the telomere length. Telomerase is normally inactive in most somatic cells but telomerase activity is observed in malignancies. In this study telomerase activity was analyzed in patients with chronic myeloid leukemia (CML) and lymphoma by PCR and ELISA. This approach combines highly specific amplification of the telomerase-mediated elongation products with nonradioactive detection in a highly sensitive photometric ELISA. The PCR products were also analyzed by Southern blotting. The telomerase-specific PCR products were seperated by electrophoresis and transferred to a nylon membrane with subsequent detection of the biotinylated amplificates. High activity levels were detected in 17 CML ( 34%) patients. On the other hand, no activity was observed in lymphoma patients. An increase in the shorter telomeric bands was observed in CML patients who displayed a high level of telomerase activity. In contrast to the low enzyme activity, evidence of telomeric repeats were also found in some lymphoma patients by Southern blotting. This may indicate that lymphoma cells may make use of different pathways for maintaining the length of their telomeres.
