Investigation of chromosome 21 aneuploidies in breast fibroadenomas by fluorescence in situ hybridisation.

Fibroadenoma (FA) is a benign breast tumour that occurs in about 25% of women. Cytogenetic studies suggest that numerical chromosomal aberrations may contribute to tumorigenesis, but chromosomal instability is still poorly characterised in breast cancer. The aim of this study was to investigate numerical alterations of chromosome 21 in 15 breast FAs. All samples were analysed by classical cytogenetics and by fluorescence in situ hybridisation (FISH) for chromosome 21 DNA sequences. Classical cytogenetics analysis showed that all cells were diploidies with modal number varying between 43 and 47 chromosomes, and clonal chromosome alterations in 46.7% of tumours. Clonal numerical alterations involved, preferentially, chromosomes 8, 10, 12, 16 and 21. FISH analysis showed a statistically significant difference for chromosome 21 monosomy between seven samples and control group. This monosomy varied from 24.5% to 43.5% of analysed cells. The presence of chromosomal alterations in FAs may be a consequence of the proliferation process and is probably not related to the aetiology of this type of lesion. The study of benign proliferations and comparison with chromosome alterations in their malignant counterparts should result in an understanding of the genes acting in cell proliferation alone and those that cause these cells to both undergo malignant transformation and become invasive.

Aneuploidy of chromosome 8 detected by fluorescence in situ hybridisation in ACP01 cell line gastric adenocarcinoma.

Gastric cancer is the third most frequent type of neoplasia and the second most important cause of death in the world. ACP01 is the first gastric adenocarcinoma cell line developed in Brazil. To evaluate chromosomal aberrations implicated in gastric carcinogenesis, we analysed three different passages (6th, 12th and 35th) of ACP01 cell line by fluorescence in situ hybridisation using chromosome 8 alpha-satellite probe. Most of the chromosome 8 alterations found involved a numerical increase of this chromosome. Chromosome 8 trisomy was detected in all cases, varying from 37% (6th passage) to 67% (35th passage), and chromosome 8 tetrasomy (also observed in all passages) varied from 2.5% (6th passage) to 30% (35th passage). The presence of five signals for chromosome 8 was observed in all passages with the highest frequency found in the 12th passage (20%). Our results confirm that trisomy of chromosome 8 is a common biological phenomenon in adenocarcinoma of stomach and can be used as a gastric mucosa malignancy marker. Although gastric tumours are frequent neoplasias, papers on their cytogenetics are scarce in the literature. It is, therefore, necessary to conduct new studies aiming to identify peculiar genetic characteristics of a tumour, which might help in diagnosis and prognosis of this disease, besides allowing more accurate therapeutic conduct to be established.

Interleukin-6 polymorphism and Helicobacter pylori infection in Brazilian adult patients with chronic gastritis.

Helicobacter pylori is recognised as the most common cause of chronic active gastritis and this bacterium is also an important pathogenic factor in peptic ulcer disease. The biological factors that influence clinical outcome in H. pylori infection have been extensively studied. In addition to immunological factors in the host, bacterial virulence determinants in H. pylori strains are likely to play a crucial role in gastric cancer development. Singlenucleotide polymorphisms at the 5' flanking region of the interleukin (IL)-6 gene promoter (G or C at -174 base) have been identified and individuals with the G allele at position -174 have been shown to produce higher levels of IL-6 than those with the C/C genotype. The mucosal levels of IL-6 were reported to be increased in H. pylori-associated gastritis. The present study was conducted to examine any relationship between inflammatory cytokine polymorphisms and the inflammatory process in mucosa infected by H. pylori. In our study we did not find any association between the C and G alleles in adult patients with chronic gastritis and inflammatory process in gastric mucosa.

Helicobacter pylori and cagA and vacA gene status in children from Brazil with chronic gastritis.

Helicobacter pylori has been shown to be strongly associated with chronic gastritis, gastric and duodenal ulceration, and is a risk factor for gastric carcinoma. Histology, urease, culture, and polymerase chain reaction have been employed as for H. pylori diagnostic methods, pre and post treatment or during follow-up of dyspeptic adult individuals referred for endoscopy. In order to obtain a more-sensitive and specific method for H. pylori detection, we evaluated gastric body and antrum biopsies of 134 consecutive Brazilian consecutive dyspeptic children aged 1-16 years by rapid urease test, histology and polymerase chain reaction using two pairs of oligonucleotides. Our results indicated that polymerase chain reaction with Southern blotting and hybridization with specific chemiluminescent probes increased the number of positive H. pylori patients by 35%. The genotyping of H. pylori strains directly from gastric biopsy using the same nucleic acid methodology revealed that there is no association of chronic gastritis in our infant patients with vacA s1 and the presence of the cagA gene. These data suggest an initial infection of children with normal mucosa and probably others factors than vacA s1 genotype or the presence of the cagA gene are associated with the onset of gastric disease. Altogether, our results reinforce the need for using more sensitive diagnostic methods in order to understand the role of H. pylori in the genesis of gastric disease in children and its progression in adults.

Alzheimer's disease and ageing: a chromosomal approach.

Alzheimer's disease (AD) is the most common type of dementia in elderly people. Interrelations between AD and senescence have been the subject of many studies. Some researchers have suggested that chromosomal alterations may be involved in the etiology or pathogenesis of AD. We present cytogenetic findings in patients with Alzheimer's disease, normal elderly controls and young controls. Aneuploidy, premature centromere division, polyploidy and C-anaphase, were analysed and the results suggest that the cytogenetic alterations observed are inherent to the cellular ageing process and not specifically related to Alzheimer's disease.