RESUMO
To assess if mitochondrial DNA (mtDNA) variants are associated with mutations in BRCA susceptibility genes and to investigate the possible role of mitochondrial alterations as susceptibility markers in familial breast cancer (BC), 22 patients with or without BRCA1/BRCA2 mutations, 14 sporadic BC patients and 20 healthy subjects were analyzed. In the D-loop and in the MTND4 region, variants significantly associated with BRCA1 carriers were identified. Moreover, examination of mitochondrial haplogroups revealed X as the most significantly frequent haplogroup in BRCA1 carriers (P=0.005), and H as significantly linked to BRCA2 carriers (P=0.05). Our data suggest the involvement of the mitochondrial genome in the pathogenetic and molecular mechanism of familial BC disease.
Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/congênito , DNA Mitocondrial/genética , NADH Desidrogenase/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Predisposição Genética para Doença , Variação Genética , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNARESUMO
Mitochondrial genome and functional alterations are related to various diseases including cancer. In all cases, the role of these organelles is associated with defects in oxidative energy metabolism and control of tumor-induced oxidative stress. The present study examines the involvement of mitochondrial DNA in cancer and in particular in breast cancer. Furthermore, since mitochondrial DNA is maternally inherited, hereditary breast cancer has been focused on.
RESUMO
BACKGROUND: Hepatozoon canis is a widespread tick-borne protozoan affecting dogs. The diagnosis of H. canis infection is usually performed by cytology of blood or buffy coat smears, but this method may not be sensitive. Our study aimed to evaluate the best method to achieve a parasitological diagnosis of H. canis infection in a population of receptive young dogs, previously negative by cytology and exposed to tick infestation for one summer season. RESULTS: A total of 73 mongrel dogs and ten beagles younger than 18 months of age, living in an animal shelter in southern Italy where dogs are highly infested by Rhipicephalus sanguineus, were included in this study. In March-April 2009 and in October 2009, blood and bone marrow were sampled from each dog. Blood, buffy coat and bone marrow were examined by cytology only (at the first sampling) and also by PCR for H. canis (second sampling). In March-April 2009, only one dog was positive for H. canis by cytological examination, whereas in October 2009 (after the summer season), the overall incidence of H. canis infection by cytological examinations was 43.9%. Molecular tests carried out on samples taken in October 2009 showed a considerably higher number of dogs positive by PCR (from 27.7% up to 51.2% on skin and buffy coat tissues, respectively), with an overall positivity of 57.8%. All animals, but one, which were positive by cytology were also PCR-positive. PCR on blood or buffy coat detected the highest number of H. canis-positive dogs displaying a sensitivity of 85.7% for both tissues that increased up to 98% when used in parallel. Twenty-six (74.8%) out of the 28 H. canis-positive dogs presented hematological abnormalities, eosinophilia being the commonest alteration observed. CONCLUSIONS: The results suggest that PCR on buffy coat and blood is the best diagnostic assay for detecting H. canis infection in dogs, although when PCR is not available, cytology on buffy coat should be preferred to blood smear evaluation. This study has also demonstrated that H. canis infection can spread among young dogs infested by R. sanguineus and be present in the majority of the exposed population within 6 months.