Epigenetic silencing of the tumor suppressor genes SPI1, PRDX2, KLF4, DLEC1, and DAPK1 in childhood and adolescent lymphomas

• Published in: Pediatric hematology and oncology Vol. 35; no. 2; pp. 131 - 144
• Main Authors: Özdemir, İhsan, Pınarlı, Faruk Güçlü, Pınarlı, Ferda Alpaslan, Aksakal, F. Nur Baran, Okur, Arzu, Uyar Göçün, Pınar, Karadeniz, Ceyda
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 17.02.2018
• Subjects: cancer genetics; CDKN2A; DAPK1; DLEC1; DNA methylation; FOXO1; KLF4; Lymphomas; PRDX2; SPI1; PRDX2; SPI1; cancer genetics; CDKN2A; DAPK1; DNA methylation; DLEC1; Lymphomas; KLF4; FOXO1
• ISSN: 0888-0018; 1521-0669
• DOI: 10.1080/08880018.2018.1467986

The aim of the study was to investigate the expression and methylation status of seven distinctive genes with tumor suppressing properties in childhood and adolescent lymphomas. A total of 96 patients with Hodgkin Lymphoma (HL, n = 41), Non-Hodgkin Lymphoma (NHL, n = 15), and reactive lymphoid hyperplasia (RLH, n = 40, as controls) are included in the research. The expression status of CDKN2A, SPI1, PRDX2, DLEC1, FOXO1, KLF4 and DAPK1 genes were measured with QPCR method after the RNA isolation from paraffin blocks of tumor tissue and cDNA conversion. DNA isolation was performed from samples with low gene expression followed by methylation PCR study specific to promoter regions of these genes. We found that SPI1, PRDX2, DLEC1, KLF4, and DAPK1 genes are significantly less expressed in patient than the control group (p = 0.0001). However, expression of CDKNA2 and FOXO1 genes in the patient and control groups were not statistically different. The methylation ratios of all genes excluding the CDKN2A and FOXO1 were significantly higher in the HL and NHL groups than the controls (p = 0.0001). We showed that SPI1, PRDX2, DLEC1, KLF4 and DAPK1 genes are epigenetically silenced via hypermethylation in the tumor tissues of children with HL and NHL. As CDKN2A gene was not expressed in both patient and control groups, we conclude that it is not specific to malignancy. As FOXO1 gene was similarly expressed in both groups, its relationship with malignancy could not be established. The epigenetically silenced genes may be candidates for biomarkers or therapeutic targets in childhood and adolescent lymphomas.