Dataset Information

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.

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.

SUBMITTER: Leite C

PROVIDER: S-EPMC5590036 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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 C Delmonico Lucas L Alves Gilda G Gomes Romario José RJ Martino Mariana Rodrigues MR da Silva Aline Rodrigues AR Moreira Aline Dos Santos ADS Maioli Maria Christina MC Scherrer Luciano Rios LR Bastos Elenice Ferreira EF Irineu Roberto R Ornellas Maria Helena MH

Biomedical reports 20170809 4

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 h ...[more]

PMID: 28928972

Similar Datasets

Project description:In human and mouse, the promoter of the KRAS gene contains a nuclease hypersensitive polypurine-polypyrimidine element (NHPPE) that is essential for transcription. An interesting feature of the polypurine G-rich strand of NHPPE is its ability to assume an unusual DNA structure that, according to circular dichroism (CD) and DMS footprinting experiments, is attributed to an intramolecular parallel G-quadruplex, consisting of three G-tetrads and three loops. The human and mouse KRAS NHPPE G-rich strands display melting temperature of 64 and 73 degrees C, respectively, as well as a K+-dependent capacity to arrest DNA polymerase. Photocleavage and CD experiments showed that the cationic porphyrin TMPyP4 stacks to the external G-tetrads of the KRAS quadruplexes, increasing the T(m) by approximately 20 degrees C. These findings raise the intriguing question that the G-quadruplex formed within the NHPPE of KRAS may be involved in the regulation of transcription. Indeed, transfection experiments showed that the activity of the mouse KRAS promoter is reduced to 20% of control, in the presence of the quadruplex-stabilizing TMPyP4. In addition, we found that G-rich oligonucleotides mimicking the KRAS quadruplex, but not the corresponding 4-base mutant sequences or oligonucleotides forming quadruplexes with different structures, competed with the NHPPE duplex for binding to nuclear proteins. When vector pKRS-413, containing CAT driven by the mouse KRAS promoter, and KRAS quadruplex oligonucleotides were co-transfected in 293 cells, the expression of CAT was found to be downregulated to 40% of the control. On the basis of these data, we propose that the NHPPE of KRAS exists in equilibrium between a double-stranded form favouring transcription and a folded quadruplex form, which instead inhibits transcription. Such a mechanism, which is probably adopted by other growth-related genes, provides useful hints for the rational design of anticancer drugs against the KRAS oncogene.

Dataset Information

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.

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets