RT Journal Article
SR Electronic
T1 Tissue methylation and demethylation influence translesion synthesis DNA polymerases (TLS) contributing to the genesis of chromosomal abnormalities in myelodysplastic syndrome
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 85
OP 93
DO 10.1136/jclinpath-2020-207131
VO 75
IS 2
A1 Gabrielle Melo Cavalcante
A1 Daniela Paula Borges
A1 Roberta Taiane Germano de Oliveira
A1 Cristiana Libardi Miranda Furtado
A1 Ana Paula Negreiros Nunes Alves
A1 Alceu Machado Sousa
A1 Dayrine Silveira de Paula
A1 Francisco Dário Rocha Filho
A1 Silvia Maria Meira Magalhães
A1 Howard Lopes Ribeiro-Jr
A1 Ronald Feitosa Pinheiro
YR 2022
UL http://jcp.bmj.com/content/75/2/85.abstract
AB Aims DNA methylation has its distribution influenced by DNA demethylation processes with the catalytic conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Myelodysplastic syndrome (MDS) has been associated with epigenetic dysregulation of genes related to DNA repair system, chronic immune response and cell cycle.Methods We evaluated the tissue DNA methylation/hydroxymethylation in bone marrow trephine biopsies of 73 patients with MDS, trying to correlate with the mRNA expression of 21 genes (POLH, POLL, REV3L, POLN, POLQ, POLI, POLK, IRF-1, IRF-2, IRF-3, IRF-4, IRF-5, IRF6, IRF-7, IRF-8,IRF-9, MAD2, CDC20, AURKA, AURKB and TPX2).Results The M-score (5mC) was significantly higher in patients with chromosomal abnormalities than patients with normal karyotype (95% CI –27.127779 to –2.368020; p=0.022). We observed a higher 5mC/5hmC ratio in patients classified as high-risk subtypes compared with low-risk subtypes (95% CI –72.922115 to –1.855662; p=0.040) as well as patients with hypercellular bone marrow compared with patients with normocellular/hypocellular bone marrow (95% CI –69.189259 to –0.511828; p=0.047) and with the presence of dyserythropoiesis (95% CI 17.077703 to 51.331388; p=0.001). DNA pols with translesion activity are significantly influenced by methylation. As 5mC immunoexpression increases, the expressions of POLH (r=−0.816; r2 =0.665; p=0.000), POLQ (r=−0.790; r2=0.624; p=0.001), PCNA (r=−0.635; r2=0.403; p=0.020), POLK (r=−0.633; r2=0.400; p=0.036 and REV1 (r=−0.578; r2=0.334; p=0.049) decrease.Conclusions Our results confirm that there is an imbalance in the DNA methylation in MDS, influencing the development of chromosomal abnormalities which may be associated with the low expression of DNA polymerases with translesion synthesis polymerases activity.All data relevant to the study are included in the article or uploaded as supplemental information.