Leucemia mieloide aguda familiar

• Autor(a) principal: Baptista, Renata Lyrio Rafael
• Data de Publicação: 2018
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/8627
• topic: Familial AML; Whole exome sequencing; GATA2; CEBPA; RUNX1; TERC; TERT; LMA familiar; Sequenciamento de última geração; Exoma; GATA2; CEBPA; RUNX1; TERT; TERC; Leucemia aguda Aspectos genéticos; Mutagênese; Leucemia Mieloide Aguda; Sequenciamento Completo do Exoma; CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA

Introduction: Although most cases of AML are sporadic, a small subgroup is associated with the presence of germ mutations. The 2016 review of the WHO Classification of 2008 included these cases in a session of myeloid neoplasia with presence of germ mutations. These patients should have a different management since the indication of related allogeneic HSCT makes it mandatory to exclude mutation in the donor sibling. In addition, family members should receive genetic counseling. Objectives: a) To establish the mutational status of the CEBPA, RUNX1, GATA2, TERT, TERC genes in patients with AML undergoing allo-HSCT in CEMO-INCA. During this work, a pair of twins discordant for the diagnosis of AML was identified. The rarity of this fact and the potential use of the model to try to understand the pathogenesis of AML lead to another goal to be developed; b) To evaluate the exome of identical twin siblings discordant for the diagnosis of AML identified in the studied cohort. Methods: The detection of mutations in the genes RUNX1, CEBPA, GATA2, TERT and TERC at 58 patients with the diagnosis of AML was performed with the implementation of the MLPA (Multiplex Ligation-dependent Probe Amplification). The evaluation of exomes was performed through bioinformatic analysis. Results: The evaluation of the mutational status of the CEBPA, RUNX1, GATA2, TERT, TERC genes did not identify any mutation. Comparison of the exomes of the identical twin discordant to AML identified 9 genes mutated in the patient and 2 genes mutated in the healthy sibling with possible clinical relevance. Genes HJURP, ABCE1, PCDHA11, AJM1, TAS2R19, AMER2, FNDC3A, SIN3A and L1CAM are mutated in the patient. RBM5 and ATXN3 are mutated in the health twin. Conclusion: At the exome analysis of the discordant twins pair in AML the mutations found in here could be the result of genetic instability lead by malignance. More experiments are needed to confirm the role of each mutation found in discordance between the pair of twins in this initial genetic screening.