title: Influence of functional polymorphisms in DNA repair genes of myelodysplastic syndrome.
abstract: Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell (HSC) malignances characterized by peripheral cytopenias and predisposition to acute myeloid leukemia transformation. Several studies show that the MDS pathogenesis is a complex and heterogeneous process that involves multiple steps through a sequence of genetic lesions in the DNA which lead to functional changes in the cell and the emergence and subsequent evolution of pre-malignant clone. Double strand breaks (DSB) lesions are the most severe type of DNA damage in HSCs, which, if not properly repaired, might contribute to the development of chromosomal abnormalities, which in turn may lead to leukemia development. We assessed the mRNA expression levels of ATM, BRCA1, BRCA2, RAD51, XRCC5, XRCC6 and LIG4 genes in bone marrow samples of 47 MDS patients in order to evaluate the association with functional polymorphisms rs228593, rs4793191, rs9567623, rs1801320, rs3835, rs2267437 and rs1805388, respectively, and try to detect clinical associations. We found that the rs228593, rs2267437 and rs1805388 functional polymorphisms probably alter the level of expression of the ATM, XRCC6 and LIG4 genes, respectively, being important in the maintenance of genomic instability in MDS.
authors: Cancer Cytogenomic Laboratory, Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil. Electronic address: howard.lrj@gmail.com.
authors: Howard Lopes
authors: HL
authors: Ribeiro
authors: Cancer Cytogenomic Laboratory, Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil. Electronic address: allanrsm@gmail.com.
authors: Allan Rodrigo
authors: AR
authors: Soares Maia
authors: Cancer Cytogenomic Laboratory, Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil. Electronic address: mariliabraga20@gmail.com.
authors: Marília Braga
authors: MB
authors: Costa
authors: Cancer Cytogenomic Laboratory, Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil. Electronic address: izabellefarias27@hotmail.com.
authors: Izabelle Rocha
authors: IR
authors: Farias
authors: Cancer Cytogenomic Laboratory, Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil. Electronic address: dpborges0@gmail.com.
authors: Daniela
authors: D
authors: de Paula Borges
authors: Cancer Cytogenomic Laboratory, Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil. Electronic address: tayaneoliveira.g@gmail.com.
authors: Roberta Taiane Germano
authors: RT
authors: de Oliveira
authors: Cancer Cytogenomic Laboratory, Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil. Electronic address: cordeiro.juliana@gmail.com.
authors: Juliana Cordeiro
authors: JC
authors: de Sousa
authors: Cancer Cytogenomic Laboratory, Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil. Electronic address: silviamm@ufc.br.
authors: Silvia Maria Meira
authors: SM
authors: Magalhães
authors: Cancer Cytogenomic Laboratory, Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program of Pathology, Federal University of Ceara, Fortaleza, Ceara, Brazil. Electronic address: ronaldfpinheiro@uol.com.br.
authors: Ronald Feitosa
authors: RF
authors: Pinheiro
mesh_terms: D000328:Adult; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D001853:Bone Marrow / Q000378:metabolism; D004249:DNA Damage; D000072481:DNA Ligase ATP / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D042822:Genomic Instability / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D000072200:Ku Autoantigen / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis
chemical_list: C000607893:LIG4 protein, human; D012333:RNA, Messenger; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D000072481:DNA Ligase ATP
keywords: DNA repair mechanisms genes; Double-strand DNA breaks; Gene expression; Gene polymorphisms; Myelodysplastic syndrome