Tumor DNA hypomethylation of LINE‑1 is associated with low tumor grade of breast cancer in Tunisian patients

Zeggar,Hayet Radia; How‑Kit,Alexandre; Daunay,Antoine; Bettaieb,Ilhem; Sahbatou,Mourad; Rahal,Khaled; Adouni,Olfa; Gammoudi,Amor; Douik,Hayet; Deleuze,Jean‑François; Kharrat,Maher

doi:10.3892/ol.2020.11745

Tumor DNA hypomethylation of LINE‑1 is associated with low tumor grade of breast cancer in Tunisian patients

Authors:
- Hayet Radia Zeggar
- Alexandre How‑Kit
- Antoine Daunay
- Ilhem Bettaieb
- Mourad Sahbatou
- Khaled Rahal
- Olfa Adouni
- Amor Gammoudi
- Hayet Douik
- Jean‑François Deleuze
- Maher Kharrat
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Affiliations: University of Tunis El Manar, Faculty of Medicine of Tunis, LR99ES10 Human Genetics Laboratory, 1007 Tunis, Tunisia, Laboratoire de Génomique, Fondation Jean Dausset‑CEPH, Centre d'Etude du Polymorphisme Humain, 75010 Paris, France, Department of Immunohistocytology, Salah Azaïz Cancer Institute, 1006 Tunis, Tunisia, Laboratoire de Biostatistique, Fondation Jean Dausset‑CEPH, Centre d'Etude du Polymorphisme Humain, 75010 Paris, France, Service de Chirurgie Carcinologique, Institut Salah Azaiz de Tunis, 1006 Tunis, Tunisia
Published online on: June 17, 2020 https://doi.org/10.3892/ol.2020.11745
Pages: 1999-2006

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Abstract

DNA hypomethylation of long interspersed repetitive DNA retrotransposon (LINE‑1) and Alu repeats elements of short interspersed elements family (SINEs) is an early event in carcinogenesis that causes transcriptional activation and leads to chromosomal instability. In the current study, DNA methylation levels of LINE‑1 and Alu repeats were analyzed in tumoral tissues of invasive breast cancer in a Tunisian cohort and its association with the clinicopathological features of patients was defined. DNA methylation of LINE‑1 and Alu repeats were analyzed using pyrosequencing in 61 invasive breast cancers. Median values observed for DNA methylation of LINE‑1 and Alu repeats were considered as the cut‑off (59.81 and 18.49%, respectively). The results of the current study demonstrated a positive correlation between DNA methylation levels of LINE‑1 and Alu repeats (rho=0.284; P<0.03). DNA hypomethylation of LINE‑1 was also indicated to be associated with low grade (P=0.023). To the best of our knowledge, the current study is the first study regarding DNA methylation of LINE‑1 and Alu repeats element in breast cancer of the Tunisian population. The results of the current study suggest that, since hypomethylation of LINE‑1 is associated with low grade, it could be used as a biomarker for prognosis for patients with breast cancer.

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