Screening of mutations in the additional sex combs like 1, transcriptional regulator, tumor protein p53, and KRAS proto-oncogene, GTPase/NRAS proto-oncogene, GTPase genes of patients with myelodysplastic syndrome

Leite,Carolina; Delmonico,Lucas; Alves,Gilda; Gomes,Romario  José; Martino,Mariana  Rodrigues; Silva,Aline  Rodrigues da; Moreira,Aline   dos Santos; Maioli,Maria  Christina; Scherrer,Luciano  Rios; Bastos,Elenice   Ferreira; Irineu,Roberto; Ornellas,Maria  Helena

doi:10.3892/br.2017.965

Screening of mutations in the additional sex combs like 1, transcriptional regulator, tumor protein p53, and KRAS proto-oncogene, GTPase/NRAS proto-oncogene, GTPase genes of patients with myelodysplastic syndrome

Authors:
- Carolina Leite
- Lucas Delmonico
- Gilda Alves
- Romario José Gomes
- Mariana Rodrigues Martino
- Aline Rodrigues da Silva
- Aline dos Santos Moreira
- Maria Christina Maioli
- Luciano Rios Scherrer
- Elenice Ferreira Bastos
- Roberto Irineu
- Maria Helena Ornellas
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Affiliations: Haematology Service, Pedro Ernesto University Hospital, Rio de Janeiro 20550‑170, Brazil, Circulating Biomarkers Laboratory, Faculty of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro 20550‑170, Brazil, Bioinformatics and Functional Genomic Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil, Department of Engineering and Production, Kennedy Faculty, Belo Horizonte 31535-040, Brazil, Department of Medical Genetic, Fernandes Figueira Institute, Oswaldo Cruz Foundation, Rio de Janeiro 22250-020, Brazil, Pedro II School, Realengo II Campus, Rio de Janeiro 21710-261, Brazil
Published online on: August 9, 2017 https://doi.org/10.3892/br.2017.965
Pages: 343-348

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Abstract

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal bone marrow disorders characterized by ineffective hematopoiesis, different degrees of cellular dysplasia, and increased risk of progression to acute myeloid leukemia. International Prognostic Scoring System is the gold standard for MDS classification; however, patients exhibiting different clinical behaviors often coexist in the same group, indicating that the currently available scoring systems are insufficient. The genes that have recently been identified as mutated in MDS, including additional sex combs like 1, transcriptional regulator (ASXL1), tumor protein p53 (TP53), and KRAS proto-oncogene and GTPase (KRAS)/NRAS proto-oncogene, GTPase (NRAS), may contribute to a more comprehensive classification, as well as to the prognosis and progression of the disease. In the present study, the mutations in the ASXL1, TP53 and NRAS/KRAS genes in 50 patients were evaluated by sequencing genomic bone marrow DNA. Nine patients (18%) presented with at least one type of mutation. Mutations in TP53 were the most frequent in six patients (12%), followed by ASXL1 in two patients (4%) and NRAS in one patient (2%). The nine mutations were detected in patients with low- and high-risk MDS. The screening of mutations in MDS cases contributes to the application of personalized medicine.

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