Comparative genome-wide DNA methylation analysis of colorectal tumor and matched normal tissues

Simmer, Femke; Brinkman, Arie B.; Assenov, Yassen; Matarese, Filomena; Kaan, Anita; Sabatino, Lina; Villanueva, Alberto; Huertas, Dori; Esteller, Manel; Lengauer, Thomas; Bock, Christoph; Colantuoni, Vittorio; Altucci, Lucia; Stunnenberg, Hendrik G.

doi:10.4161/epi.22562

Cited by 69 publications

(77 citation statements)

References 40 publications

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“…The spectrum of applications for NGS-based profiling includes genome-wide analysis of DNA methylation patterns, post-translational modifications of histones and the coding and non-coding transcriptome, on a genome-wide scale. The impact of epigenetic changes such as DNA methylation and histone modification has been better documented in the pathogenesis of other human diseases [33][34][35][36], while the application of genomic technologies in human PAH samples are relatively limited. To date, except for a few studies [37][38][39][40], the approaches employed to delineate the disease mechanisms in PAH have not provided a global perspective of the molecular network underlying the disease phenotype.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives

2016

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Pulmonary arterial hypertension (PAH) is a severe and progressive disease, characterised by high pulmonary artery pressure that usually culminates in right heart failure. Recent findings of alterations in the DNA methylation state of superoxide dismutase 2 and granulysin gene loci; histone H1 levels; aberrant expression levels of histone deacetylases and bromodomain-containing protein 4; and dysregulated microRNA networks together suggest the involvement of epigenetics in PAH pathogenesis. Thus, PAH pathogenesis evidently involves the interplay of a predisposed genetic background, epigenetic state and injurious events. Profiling the genome-wide alterations in the epigenetic mechanisms, such as DNA methylation or histone modification pattern in PAH vascular cells, may explain the great variability in susceptibility and disease severity that is frequently associated with pronounced remodelling and worse clinical outcome. Moreover, the influence of genetic predisposition and the acquisition of epigenetic alterations in response to environmental cues in PAH progression and establishment has largely been unexplored on a genome-wide scale. In order to gain insights into the molecular mechanisms leading to the development of PAH and to design novel therapeutic strategies, high-throughput approaches have to be adopted to facilitate systematic identification of the disease-specific networks using next-generation sequencing technologies, the application of these technologies in PAH has been relatively trivial to date. @ERSpublications An epigenetic component is hypothesised in PAH: an overview of the current literature and future perspectives

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Section: Discussionmentioning

confidence: 99%

Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives

2016

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“…4,5 DNA methylation of a number of genes and their significance in CRC has been reported. [1][2][3][4][5][6][7] The hypermethylation of several gene promoters including APC, p16INK4a, and TIMP3 in CRC 8,9 and other tumor suppressor genes were investigated by qualitative and quantitative approaches such as MSP, qPCR, and pyrosequencing. 10 The aberrant methylation of CpG islands within gene promoters and/or first exonic/intronic regions is a recognized epigenetic event that leads to transcriptional silencing of corresponding tumor suppressor genes in CRC and other cancers.…”

Section: Introductionmentioning

confidence: 99%

“…Regardless of the biological consequences of methylation-induced silencing of tumor suppressor genes, this epigenetic alteration constitutes molecular signatures that can serve as promising biomarkers for early detection. 5,6 Many genes are silenced by aberrant methylation in CRC, such genes have the potential to become useful biomarkers for early detection of colorectal neoplasia but need first to be validated using genome wide studies. 5,6,11,12 The ability to detect aberrant DNA methylation from a wide range of biological specimens, including blood, stool, and paraffin-embedded formalin-fixed tissue, highlights its robustness and excellent potential to detect markers of clinical utility.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the identification of the epigenetically deregulated signaling pathways may provide prudent means of selecting CRC patients who will be particularly responsive to targeted therapies. [5][6][7][8]16 We have shown that the prevalence and the incidence of colorectal cancer in the African American population is worse than the general population, [17][18][19][20][21][22][23][24] and studies are underway to investigate the risk factors for this disparity. Therefore, epigenetic determinants are part of the parameters that need to be investigated in CRC from AA population.…”

Section: Introductionmentioning

confidence: 99%

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DNA methylome profiling identifies novel methylated genes in African American patients with colorectal neoplasia

et al. 2014

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“…Many studies have identified ASE and imprinting patterns for genes with important biological functions. For example, ASE has been consistently associated with cancer and disease-causing genes (Meyer et al, 2008;Simmer et al, 2012;Walker et al, 2012;Wei et al, 2013), such as Prader-Willi syndrome in humans (Wu et al, 2012). Subsequently, complex traits and diseases can be affected by genes displaying patterns of ASE, with or without parentof-origin effects (POE), and these expression patterns may result in phenotypic variation.…”

Section: Introductionmentioning

confidence: 99%

Allele- and parent-of-origin-specific effects on expression of the KCNJ11 gene: A candidate for meat tenderness in cattle

Souza¹,

Niciura²,

Tizioto³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. In contrast to the Mendelian inheritance model, parental alleles can contribute unequally to gene expression, which may result in phenotypic variance among individuals and bias in the predicted additive effect of molecular markers associated with production traits. Given the need to understand the effects of allelic variation and parentof-origin effects on the expression of genes with a commercial interest in cattle, we analyzed the expression of KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11), which was previously described as a functional candidate gene for meat tenderness. Allelespecific and parent-of-origin-dependent expression of this gene were assessed in bovine muscle using the rs379610823 single nucleotide polymorphism as a reference. Biallelic expression was observed; however, the T allele was expressed at significantly higher levels than the C allele. Furthermore, increased expression of KCNJ11 was found in animals harboring the maternal T allele. This study is the first to describe the differential allelic expression of bovine KCNJ11. Our findings are important for understanding the mechanisms that underlie the pattern of KCNJ11 expression and its potential impact on the phenotypic variation of meat tenderness in Nelore beef cattle. This reinforces the need for further investigation of allelic-and parent-oforigin expression deviation in genetic markers eligible for the selection of target traits.

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Comparative genome-wide DNA methylation analysis of colorectal tumor and matched normal tissues

Cited by 69 publications

References 40 publications

Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives

Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives

DNA methylome profiling identifies novel methylated genes in African American patients with colorectal neoplasia

Allele- and parent-of-origin-specific effects on expression of the KCNJ11 gene: A candidate for meat tenderness in cattle

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