Epigenetic Biomarker Development

Bock, Christoph

doi:10.2217/epi.09.6

Cited by 112 publications

(75 citation statements)

References 111 publications

(137 reference statements)

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“…In this study the correlation between methylation of MAP9 gene and age of patients, disease stage, the status of the biomarkers such as, ER, PR, and HER2 in 30 breast cancers were evaluated [32].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of DNA Methylation of MAP9 Gene in Breast Cancer as Epigenetic Biomarker

Dehbid¹,

Aleyasin²,

Vaziri³

2016

J Mol Biomark Diagn

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IntroductionCancer is abnormal cell divisions without control and ability to invade other tissues. Most cancers are named for the organ or type of cell in which they start [1]. Breast cancer is a type of cancer that starts in the breast tissue. The causes are unknown, although there are some evidence that epigenetic factors may be one of the risk factors for breast cancer [2].The modern definition of epigenetics is the study of heritable changes in gene expression that are not caused by changes in DNA sequence [3]. DNA methylation of the epigenetic mechanisms involved in numerous phenomena such as parental imprinting, Growth and embryonic differentiation, X Chromosome inactivation and inhibition of gene transcription [4][5][6]. The methyl group (CH 3 ) is transfered from S-adenosylmethionine (SAM) to CPG dinucleotide on the 5-carbon position of cytosine by methyltransferases [7]. DNA Methylation occurs in intragenic, intergenic, 5› gene upstream and 3› gene downstream regions, which create a pattern of DNA methylation in genome [8].Many studies have shown that methylation pattern abnormalities lead to the creation of cancer [9], and hypermethylation and hypomethylation of DNA happen in early and developing stages of various types of cancers. They can be considered as epigenetic biomarker of cancer in the human DNA [10,11]. In other words, cancer biomarker refers to indication of the presence of cancer in the body [12]. In cancer research and medicine, usage of biomarkers is including: Diagnosis (to help diagnose conditions, as in the case of identifying early stage cancers); Prognosis (to indicate how aggressive a condition is, as in the case of determining a patient's ability to fare in the absence of treatment); Prediction (to predict how well a patient will respond to treatment) [13].Genetics, epigenetics, proteomics and glycomics can be used for cancer biomarkers [12]. In this study, we examined the Microtubule-Associated Protein 9 (MAP9) gene methylation as an epigenetic biomarker of cancer. Human MAP9 gene is also called ASAP, which is located on chromosome 4q32.1 and on the negative strand DNA [14]. The gene encodes MAP9 protein that it's C-terminal is associated with α-tubulin at all phases of the cell cycle. MAP9 protein is required for spindle function, bipolar spindle assembly, mitotic progression, and cytokinesis. It may also serve to stabilize interphase microtubules [15][16][17].Accurate transfer of genetic information plays essential roles for the survival of living organisms. DNA damage is induced by endogenous or exogenous factors. The tumor suppressor protein p53 is a central regulator of cell cycle arrest and apoptosis in the response to genotoxic stress. The inappropriate p53 activation is prevented through a network of tight controls in unstressed cells. The p53 protein is rapidly stabilized AbstractBackground: Recent findings indicate epigenetic modifications as key factors in breast carcinogenesis. The abnormal methylation patterns of genes are among the consequences of epigenetic changes...

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Section: Discussionmentioning

confidence: 99%

Evaluation of DNA Methylation of MAP9 Gene in Breast Cancer as Epigenetic Biomarker

Dehbid¹,

Aleyasin²,

Vaziri³

2016

J Mol Biomark Diagn

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“…[144][145][146] • Epigenetic changes in cancer cells not only provide novel targets for drug therapy but also offer unique prospects for cancer diagnostics, through the study of gene expression, the evaluation of histone modifications and chromatin protein composition, and also the analysis of the promoter DNA methylation status. 139,[147][148][149] • Finally and more importantly, by shifting the focus on the environment and the complex interactions between the environmental regulation of gene expression and the genome, rather than on the genes themselves, epigenetics stresses the importance of cancer prevention and the changes of most of our common lifestyles, including diet and behaviour. …”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

The Epigenetic Origin of Retinoblastoma

Milardi¹,

Loré²,

Grasso³

2012

European Ophthalmic Review

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The aim of the present review is to give new insights into the pathogenesis of retinoblastoma, by applying the principles of epigenetics to the study of clinical, epidemiological and biological data concerning the disease. As an emerging new scientific approach linking the genome to the environment, epigenetics, can not only explain the inconsistencies of the mutational ('two hit') model in the genesis of retinoblastoma, but also open new outstanding scenarios in the fields of diagnosis, treatment and prevention of this eye tumour and cancer in general. After more than four decades of predominance of the 'genetic' theory, this review represents, to the authors' knowledge, the first attempt to look at retinoblastoma from the point of view of epigenetics. The epigenetic model in the genesis of retinoblastoma, proposed herein, emphasises the role of environment and its interactions with the genome, in generating retinoblastoma in young children. Environmental toxicants, including, among others, radiations, wrong diets and infectious diseases, all play a major role in conditioning the degree of DNA methylation (one of the leading mechanisms of epigenetic gene regulation) in embryos and foetuses during pregnancy, thus leading to stable, functional alterations of the genome, which can be transmitted from one generation to the next, thus mimicking a hereditary disease. An accurate analysis of the currently available literature on both retinoblastoma and epigenetics, coupled with the knowledge of the variegated phenotypic expression of the disease, can easily lead to the conclusion that retinoblastoma is an epigenetic, rather than a genetic disease.

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“…At the moment, only a very few DNA methylation based biomarkers have been implemented in clinical practice. The review on biomarker development by Christoph Bock pro vides some guidelines and bioinformatic tools that might help to accelerate the process through the prioritization of candidate genes and auto mated optimization of assay [6]. One common way to assess the functional importance of genes identified in genomewide studies as inactivated …”

Section: Epigenomics Deal With Very Different Topics It Becomes Evidmentioning

confidence: 99%