Pediatric pineal germinomas: Epigenetic and genomic approach

Pérez-Ramírez, Monserrat; Hernández-Jiménez, Alejo Justino; Guerrero-Guerrero, Armando; Siordia-Reyes, Alicia Georgina; Hernández-Caballero, Marta Elena; García‐Méndez, Antonio; León, Fernando Chico-Ponce de; Salamanca-Gómez, F; García-Hernández, Normand

doi:10.1016/j.clineuro.2016.11.012

Cited by 10 publications

(4 citation statements)

References 33 publications

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“…44 CDCA7L has been associated with hepatocellular carcinoma and found to have altered methylation and gene expression in pediatric pineal tumors. 45 A tumor-suppressive role of RBM47 has been reported in colorectal and breast cancer 46,47 and in lung adenocarcinomas. 48 Validation of the aberrant methylation of these genes' promoter region in an independent cohort in the future will be important for defining CIMP in NFPanNET subtypes.…”

Section: Discussionmentioning

confidence: 99%

Distinct genome‐wide methylation patterns in sporadic and hereditary nonfunctioning pancreatic neuroendocrine tumors

Tirosh

Mukherjee

Lack

et al. 2019

Cancer

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BACKGROUND: Aberrant methylation is a known cause of cancer initiation and/or progression. There are scant data on the genome-wide methylation pattern of nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) and sporadic and hereditary NFPanNETs. METHODS: Thirty-three tissue samples were analyzed: they included samples from sporadic (n = 9), von Hippel-Lindau (VHL)-related (n = 10), and multiple endocrine neoplasia type 1 (MEN1)-related NFPanNETs (n = 10) as well as normal islet cells (n = 4) for comparison. Genome-wide CpG methylation profiling was performed with the Infinium MethylationEPIC BeadChip assay and was analyzed with R-based tools. RESULTS: In unsupervised hierarchical clustering, sporadic and MEN1-related NFPanNETs clustered together, and the VHL group was in a separate cluster. MEN1-related NFPanNETs had a higher rate of hypermethylated CpG sites in comparison with sporadic and VHL-related tumor groups. Differentially methylated region analysis confirmed the higher rate of hypermethylation in MEN1-related tumors. Moreover, in an integrated analysis of gene expression data for the same tumor samples, downregulated gene expression was found in most genes that were hypermethylated. In a CpG island methylator phenotype analysis, 3 genes were identified and confirmed to have downregulated gene expression: secreted frizzle-related protein 5 (SFRP5) in sporadic NFPanNETs and cell division cycle-associated 7-like (CDCA7L) and RNA binding motif 47 (RBM47) in MEN1-related NFPanNETs. CONCLUSIONS: MEN1 NFPanNETs have a higher rate of genome-wide hypermethylation than other NFPanNET subtypes. The similarity between the pathways enriched in a methylation analysis of known genes involved in NFPanNET tumorigenesis suggests a key role for aberrant methylation in the pathogenesis of NFPanNETs.

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Section: Discussionmentioning

confidence: 99%

Distinct genome‐wide methylation patterns in sporadic and hereditary nonfunctioning pancreatic neuroendocrine tumors

Tirosh

Mukherjee

Lack

et al. 2019

Cancer

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“…Pathways enriched for hypermethylated genes in tumours developing in MEN1-knockout mice included those involved in the Wnt/beta-catenin pathway, with increased beta-catenin levels secondary to loss of Sox-regulatory proteins by promoter methylation ( Yuan et al 2016 ). In PNETs from patients with MEN1, promoter methylation in two genes has been reported: cell division cycle associated 7 like and RNA-binding motif protein 47 ( Tirosh et al 2019 ), with aberrant expression reported in other malignancies, including paediatric pineal germinomas and colorectal cancer ( Perez-Ramirez et al 2017 , Rokavec et al 2017 ). Findings from these studies may be explained by menin-mediating H3K4 methylation, an active histone mark, which may protect DNA from methylation ( Cedar & Bergman 2009 ), or alternatively, menin loss may lead to increased global DNA methylation and gene specific TSG methylation ( Fig.…”

Section: Dna Methylation In Pnetsmentioning

confidence: 99%

The role of DNA methylation in human pancreatic neuroendocrine tumours

2023

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Pancreatic neuroendocrine tumours (PNETs) are the second most common pancreatic tumour. However, relatively little is known about their tumourigenic drivers, other than mutations involving the Multiple Endocrine Neoplasia 1 (MEN1), ATRX Chromatin Remodeler (ATRX), and Death Domain Associated Protein (DAXX) genes, which are found in ~ 40% of sporadic PNETs. PNETs have a low mutational burden, thereby suggesting that other factors likely contribute to their development, including epigenetic regulators. One such epigenetic process, DNA methylation, silences gene transcription via 5’methylcytosine (5mC), and this is usually facilitated by DNA methyltransferase enzymes at CpG rich areas around gene promoters. However, 5’hydroxymethylcytosine (5hmC), which is the first epigenetic mark during cytosine demethylation, and opposes the function of 5mC, is associated with gene transcription, although the significance of this remains unknown, as it is indistinguishable from 5mC when conventional bisulfite conversion techniques are solely used. Advances in array-based technologies have facilitated investigation of PNET methylomes and enabled PNETs to be clustered by methylome signatures, which has assisted in prognosis and discovery of new aberrantly regulated genes contributing to tumourigenesis. This review will discuss the biology of DNA methylation, its role in PNET development, and impact on prognostication and discovery of epigenome-targeted therapies.

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“…International Publisher over-expressed in neuronal processes [13]. In glioma, whole exome sequencing have shown somatic mutation of TRA2A in chemotherapy patients [14].…”

Section: Ivyspringmentioning

confidence: 99%

“…Meta analysis of gene profiling data showed that TRA2A up-regulation was strongly associated with liver cancer 12 . In pediatric pineal germinomas, TRA2A has consistent chromosomal changes, dys-regulated methylation patterns and is over-expressed in neuronal processes 13 . In glioma, whole exome sequencing have shown somatic mutation of TRA2A in chemotherapy patients 14 .…”

Section: Introductionmentioning

confidence: 99%

TRA2A Binds With LncRNA MALAT1 To Promote Esophageal Cancer Progression By Regulating EZH2/β-catenin Pathway

Zhao¹,

Chen²,

Cai³

et al. 2021

J. Cancer

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The RNA binding protein TRA2A, a member of the transformer 2 homolog family, plays a crucial role in the alternative splicing of pre-mRNA. However, it remains unclear whether TRA2A is involved in non-coding RNA regulation and, if so, what are the functional consequences. By analyzing expression profiling data, we found that TRA2A is highly expressed in esophageal cancer and is associated with disease-free survival and overall survival time. Subsequent gain-and loss-of-function studies demonstrated that TRA2A promotes proliferation and migration of esophageal squamous cell carcinoma and adenocarcinoma cells. RNA immunoprecipitation and RNA pull-down assay indicated that TRA2A can directly bind specific sites on MALAT1 in cells. In addition, ectopic expression or depletion of TRA2A leads to MALAT expression changes accordingly, thus modulates EZH2/β-catenin pathway. Together, these findings elucidated that TRA2A triggers carcinogenesis via MALAT1 mediated EZH2/β-catenin axis in esophageal cancer cells.

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Pediatric pineal germinomas: Epigenetic and genomic approach

Cited by 10 publications

References 33 publications

Distinct genome‐wide methylation patterns in sporadic and hereditary nonfunctioning pancreatic neuroendocrine tumors

Distinct genome‐wide methylation patterns in sporadic and hereditary nonfunctioning pancreatic neuroendocrine tumors

The role of DNA methylation in human pancreatic neuroendocrine tumours

TRA2A Binds With LncRNA MALAT1 To Promote Esophageal Cancer Progression By Regulating EZH2/β-catenin Pathway

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