| Grant number: | 11/01647-2 |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| Start date: | August 01, 2011 |
| End date: | July 31, 2013 |
| Field of knowledge: | Health Sciences - Medicine - Medical Clinics |
| Principal Investigator: | Fábio Morato de Oliveira |
| Grantee: | Fábio Morato de Oliveira |
| Host Institution: | Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
| Associated researchers: | Eduardo Magalhães Rego ; Roberto Passetto Falcão ; Rodrigo do Tocantins Calado de Saloma Rodrigues |
| Associated scholarship(s): | 11/17405-8 - EVALUATION OF GENOMIC INSTABILITY BY ANALYSIS OF THE NUCLEAR THREE-DIMENSIONAL ORGANIZATION OF TELOMERES IN MYELODYSPLASTIC SYNDROME (MDS), BP.JP |
Abstract
The evaluation of the genomic instability by strategies that apply nuclear three-dimensional (3D) reconstitution involving constrained interative (deconvolution) represents an original approach to study blood neoplasias (leukemias, lymphomas and myelodysplastic syndrome). Genes and telomeres alterations at the chromosomal level, can be evaluated by molecular cytogenetics on neoplastic cells. The chromosome analysis will illustrate the consequences of abnormalities in telomeres. The origin of these alterations and their impact on genomic instability with simultaneous cellular transformation are questions to be answered using methodologies that apply the study and 3D quantification of interphase nucleus and its subcellular structures. These data are validated independently using methods that apply molecular cytogenetics to metaphase and interphase chromosomes, including spectral karyotyping (SKY) and quantitative fluorescence in situ hybridization (qFISH) of the telomeres and genes, respectively. Thus, the goals of this investigation are to evaluate and estimate the levels of genomic instability measuring the disposition, size and frequency of aggregate telomeres and the genes AURKA, AURKB and TP53, using FISH and deconvolution methods in patients with myelodisplastic syndrome (MDS, CD34+ cells), compared with cells of healthy individuals. From the data obtained, a model of leukemic progression for MDS will be established. Considering the objectives proposed, the application of a new strategy that applies three-dimensional nuclear reconstitution will allow for the establishment of new projects with research groups that also study neoplasias in human cells or in animal models. We predict that the identification of new alterations relevant to diagnosis and prognosis will enable the development of new therapeutic strategies for the neoplasia investigated here. (AU)
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