Alterações cromossômicas inesperadas em Tayassu tajacu (Artiodactyla: tayassuidae) de cativeiros

Wild animals have been used as bioindicators in situations in which the environment was exposed to chemical agents. In general, chemical agents may induce chromosomal aberrations, such as breaks and gaps. The peccary, Tayassu tajacu is a pig relative that exhibits a very stable karyotype with the only described alterations being of the form of the X chromosome. Chromosomal gaps and breaks were observed at high frequencies during cytogenetics analyses. These alterations were observed in the chromosomes autossomics. Reviews of the literature and of the data described herein suggests that an vermifuge, the ivermectin base, was the most likely cause of these chromosomal alterations.Os animais silvestres têm sido utilizados como bioindicadores quando o ambiente é exposto a estressores químicos. Em geral, os agentes químicos podem induzir às alterações cromossômicas dos tipos falhas e quebras. Tayassu tajacu, é uma espécie aparentada dos porcos verdadeiro e apresenta uma grande estabilidade cariotípica. As únicas alterações descritas são em relação a forma do cromossomo X. Foram observadas falhas e quebras cromossômicas durante as análise citogenética. Estas alterações foram detectadas em cromossomos autossômicos. Levantamentos realizados na literatura associados as dados observados nos exemplares estudados, indicam um vermífugo, a base de ivermectina, como o possível causador dessas alterações cromossômicas

FANCD2 and BRCA1 have differential expression among the FA-BRCA genes in primary breast cancer/ Expressão diferencial de FANCD2 e BRCA1 no câncer de mama primário

The molecular pathways of DNA repair in tumors may play a role in tailoring patient therapy. The Fanconi anemia DNA repair pathway operates in the repair of DNA interstrand crosslink induced by several chemotherapeutic drugs. In this study we evaluated the expression of Fanconi anemia DNA repair genes (FANCA, C, D2, F, BRCA1 and PALB2) in 46 primary breast tumors and ten non-compromised breast samples, by Real-Time Quantitative Reverse Transcription PCR, and to correlated gene expression with breast cancer subtypes and clinico-pathological parameters. Tumor samples were classified in subtypes based on immunohistochemistry markers, and clinico-pathological parameters were obtained from the medical reports. FANCD2 was twice more expressed in tumors than in the non-compromised group (p= 0.02). BRCA1 showed a differential expression in the luminal group, three times less expressed in Luminal-B than in Luminal-A group (p= 0.01). In conclusion, the higher level of expression of FANCD2 in tumors may indicate activation of the Fanconi anemia DNA repair pathway, which has been implicated in breast carcinogenesis and in chemotherapeutic resistance. The loss of BRCA1 expression in the Luminal-B group may indicate that the use of cisplatin-based neo/adjuvant therapies is preferable, and that the use of taxol-based therapies should be avoided due to the risk of drug resistance

Characterization of MTAP gene expression in breast cancer patients and cell lines

MTAP is a ubiquitously expressed gene important for adenine and methionine salvage. The gene is located at 9p21, a chromosome region often deleted in breast carcinomas, similar to CDKN2A, a recognized tumor suppressor gene. Several research groups have shown that MTAP acts as a tumor suppressor, and some therapeutic approaches were proposed based on a tumors\ub4 MTAP status. We analyzed MTAP and CDKN2A gene (RT-qPCR) and protein (western-blotting) expression in seven breast cancer cell lines and evaluated their promoter methylation patterns to better characterize the contribution of these genes to breast cancer. Cytotoxicity assays with inhibitors of de novo adenine synthesis (5-FU, AZA and MTX) after MTAP gene knockdown showed an increased sensitivity, mainly to 5-FU. MTAP expression was also evaluated in two groups of samples from breast cancer patients, fresh tumors and paired normal breast tissue, and from formalin-fixed paraffin embedded (FFPE) core breast cancer samples diagnosed as Luminal-A tumors and triple negative breast tumors (TNBC). The difference of MTAP expression between fresh tumors and normal tissues was not statistically significant. However, MTAP expression was significantly higher in Luminal-A breast tumors than in TNBC, suggesting the lack of expression in more aggressive breast tumors and the possibility of using the new approaches based on MTAP status in TNB

Citogenética e raça: um estudo em índios Kaingáng do Paraná

Citogenética e raça: um estudo em índios Kaingáng do Paran

Microsatellite studies on an isolated population of African descent in the Brazilian state of Bahia

The African descent population of the Bananal community in the Brazilian state of Bahia (BA) was characterized as a genetic isolate and analyzed for some short tandem repeat (STR) microsatellite autosomic polymorphic loci (CSF1PO, TH01, TPOX, F13A1, FESFPS and vWA). These genetic variants were further compared to data obtained from an urban sample from the town of Jequié (BA) regarding demographic and anthropogenetic aspects. The Bananal sample comprised 32 unrelated individuals whereas Jequié was represented by 76 individuals. The Bananal Negroid Phenotypic Index (NPI) was 0.98 and the Negroid Cultural Index (NCI) 0.24. Consanguineous marriages occurred at a frequency of 34.61% and the F value was 0.0126. All six loci studied were in Hardy-Weinberg Equilibrium (p > 0.05). The genotypic and allele frequencies of the CSF1PO and vWA loci were similar. In the Bananal population the genic diversity of the THO1 locus was 66.8% and that of the F13A1 locus was 83.7%. The estimated ethnic racial admixture was 81% African and 19% Amerindian. The multiple correlation coefficient (R²) indicated adequate adaptation (99%). Total genetic variation for the six loci was 82.9% with an index of 6.7% for population subdivision (G ST' = 0.067). Anthropologic data and results obtained from the allele frequencies of the loci studied are indicative of a genetic isolate in Bananal, reminiscent of the a 'quilombo community' (i.e. one founded by run away slaves)

Association of FOSL1 copy number alteration and triple negative breast tumors

Abstract Copy number alterations (CNAs) are a frequent feature in human breast cancer, and one of the hallmarks of genomic instability. The FOSL1, GSTP1 and CCND1 genes are located at 11q13, a cytoband commonly affected by CNA in breast cancer, with relevant function in progression and invasion. Our main goal was to analyze CNAs of these genes and determine their association with breast cancer subtypes. Seventy-three cases of invasive breast tumors [52 Luminal, 7 HER2+ and 14 triple negative (TNBC) subtypes] were analyzed by TaqMan assays. CNAs were observed for all genes, with gains more frequently observed. Gains of the FOSL1 gene were observed in 71% of the cases. This gene was the only one with a statistically significant difference (p<0.001) among tumor subtypes, with increased copy number in TNBC compared to luminal and HER2+. No significant association of CNA and clinical and histopathological parameters from the patients was observed. Additional studies in larger breast cancer patient cohorts based on more refined molecular subtypes are necessary to confirm the observed association of FOSL1 gain with aggressive breast tumors phenotypes