Global DNA methylation of peripheral blood leukocytes from dogs bearing multicentric non-Hodgkin lymphomas and healthy dogs: A comparative study

8 de dezembro de 2020

Metilação global do DNA do sangue periférico leucócitos de cães com multicêntrico Linfomas não Hodgkin e cães saudáveis: um estudo comparativo

Autores

Tatiane Moreno Ferrarias Epiphanio, Nata´lia Coelho Couto de Azevedo Fernandes, Tiago Franco de Oliveira, Priscila Assis Lopes, Rodrigo Albergaria Ressio, Simone Goncalves, Nayra Villar Scattone, Marcello Vannucci Tedardi, Leslie Domenici Kulikowski, Jullian Damasceno, Ana Paula de Melo Loureiro, Maria Lucia Zaidan Dagli

Abstract

Non-Hodgkin lymphomas are among the most common types of tumors in dogs, and they
are currently accepted as comparative models of the disease in humans. Aberrant patterns
of DNA methylation seem to play a key role in the development of hematopoietic neoplasms
in humans, constitute a special mechanism of transcriptional control, and may be influenced
by genetic and environmental factors. Blood leukocyte DNA global methylation has been
poorly investigated in dogs. The aim of this study is to examine whether peripheral blood
global DNA methylation is associated with canine multicentric lymphomas. Peripheral
venous blood samples from ten healthy dogs and nine dogs bearing multicentric lymphomas
were collected, and the buffy coat was separated. Global DNA methylation was analyzed by
High Performance Liquid Chromatography (HPLC) and immunocytochemistry (ICC). In
both analyses, leukocytes from dogs with lymphoma presented lower global DNA methylation than in healthy dogs (HPLC: p = 0.027/ 5MeCyt immunoreactivity scores: p = 0.015).
Moderate correlation was observed between the results obtained by HPLC and ICC (correlation coefficient = 0.50). For the identification of differently methylated genes between both
groups, the Infinium Human Methylation (HM) EPIC BeadChip (850K) was used. Of the
853,307 CpGs investigated in the microarray, there were 34,574 probes hybridized in the
canine samples. From this total, significant difference was observed in the methylation level
of 8433 regions, and through the homologous and orthologous similarities 525 differently
methylated genes were identified between the two groups. This study is pioneer in suggesting that dogs bearing non-Hodgkin lymphoma presented DNA global hypomethylation of circulating leukocytes compared with healthy dogs. Although canine samples were used in anassay developed specifically for human DNA, it was possible to identify differently methylated genes and our results reiterate the importance of the use of peripheral blood leukocytes
in cancer research and possible new biomarkers targets.

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