DNA methylation profiling in the clinic: applications and challenges

Key Points Alterations in epigenetic marks — specifically DNA methylation — are an emerging biomarker that may be used in the decision-making process for disease diagnosis, prognosis and treatment, most notably in cancer, but there are examples in other diseases, such as type 1 diabetes. Alterations...

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Vydané v:	Nature reviews. Genetics Ročník 13; číslo 10; s. 679 - 692
Hlavní autori:	Heyn, Holger, Esteller, Manel
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 01.10.2012 Nature Publishing Group
Predmet:	631/208/176/1988 631/208/191/2018 631/208/721 Agriculture Animal Genetics and Genomics Animals Biological and medical sciences Biomarkers Biomedical and Life Sciences Biomedicine Cancer Research Clinical Laboratory Techniques - methods Clinical Laboratory Techniques - standards Datasets Disease Disease - genetics DNA DNA methylation DNA Methylation - physiology Epigenesis, Genetic - physiology Epigenetic inheritance Epigenetics Fundamental and applied biological sciences. Psychology Gene Expression Profiling - methods Gene Expression Profiling - statistics & numerical data Gene Function Genes Genetic aspects Genetics of eukaryotes. Biological and molecular evolution Genomes Health aspects Human Genetics Humans Medical diagnosis Methylation Models, Biological Molecular Targeted Therapy - methods Molecular Targeted Therapy - trends Mutation Prostate cancer review-article Spain Methylation DNA Review
ISSN:	1471-0056, 1471-0064, 1471-0064
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Abstract	Key Points Alterations in epigenetic marks — specifically DNA methylation — are an emerging biomarker that may be used in the decision-making process for disease diagnosis, prognosis and treatment, most notably in cancer, but there are examples in other diseases, such as type 1 diabetes. Alterations in epigenetic marks that are chosen as biomarkers must be carefully selected owing to the dynamic nature of these marks. These alterations may be detected in non-invasive tissues, such as serum, in addition to primary tissues and so may have advantages over genetic biomarkers. Glutathione S -transferase pi 1 ( GSTP1 ) is the best-studied example of an epigenetic biomarker for cancer diagnosis. However, additional candidates show a high potential for future clinical applications, although specificity of diagnosis is an issue, and combinatorial approaches analysing DNA methylation alterations at several genes may improve this. Single-gene approaches have identified epigenetic biomarkers that predict cancer recurrence and survival. Recently, high-resolution genome-wide technologies have shown the potential to improve this strategy with DNA methylation signatures of cancers showing high predictive capacity of disease prognosis. DNA methylation alterations may be used as biomarkers to predict response to chemotherapy strategies. O 6 -methylguanine DNA methyltransferase ( MGMT ) and breast cancer 1, early onset ( BRCA1 ) are examples of hypermethylated genes that predict a response to chemotherapy in cancer. Additional prognostic gene markers have already been identified and suggest DNA methylation profiling as a potent strategy to predict drug response. Recent advances in sequencing and array technologies, which are capable of screening DNA methylomes genome-wide at high-resolution, gave unexpected novel insights in cancer biology. They will be crucial for DNA methylation profiling and the identification of epigenetic biomarker for diagnosis, prognosis and prediction of drug response. Epigenetic alterations, notably in DNA hypermethylation, are emerging as consistent biomarkers for disease. Here, with a focus on cancer, the authors discuss the identification of these biomarkers and their use in disease diagnosis, prognosis and response to therapy. Knowledge of epigenetic alterations in disease is rapidly increasing owing to the development of genome-wide techniques for their identification. The ever-growing number of genes that show epigenetic alterations in disease emphasizes the crucial role of these epigenetic alterations — particularly DNA methylation — for future diagnosis, prognosis and prediction of response to therapies. This Review focuses on epigenetic profiling, which has started to be of clinical value in cancer and may in the future be extended to other diseases, such as neurological and autoimmune disorders.
AbstractList	Knowledge of epigenetic alterations in disease is rapidly increasing owing to the development of genome-wide techniques for their identification. The ever-growing number of genes that show epigenetic alterations in disease emphasizes the crucial role of these epigenetic alterations - particularly DNA methylation - for future diagnosis, prognosis and prediction of response to therapies. This Review focuses on epigenetic profiling, which has started to be of clinical value in cancer and may in the future be extended to other diseases, such as neurological and autoimmune disorders. Knowledge of epigenetic alterations in disease is rapidly increasing owing to the development of genome-wide techniques for their identification. The ever-growing number of genes that show epigenetic alterations in disease emphasizes the crucial role of these epigenetic alterations - particularly DNA methylation - for future diagnosis, prognosis and prediction of response to therapies. This Review focuses on epigenetic profiling, which has started to be of clinical value in cancer and may in the future be extended to other diseases, such as neurological and autoimmune disorders.Knowledge of epigenetic alterations in disease is rapidly increasing owing to the development of genome-wide techniques for their identification. The ever-growing number of genes that show epigenetic alterations in disease emphasizes the crucial role of these epigenetic alterations - particularly DNA methylation - for future diagnosis, prognosis and prediction of response to therapies. This Review focuses on epigenetic profiling, which has started to be of clinical value in cancer and may in the future be extended to other diseases, such as neurological and autoimmune disorders. Key Points Alterations in epigenetic marks — specifically DNA methylation — are an emerging biomarker that may be used in the decision-making process for disease diagnosis, prognosis and treatment, most notably in cancer, but there are examples in other diseases, such as type 1 diabetes. Alterations in epigenetic marks that are chosen as biomarkers must be carefully selected owing to the dynamic nature of these marks. These alterations may be detected in non-invasive tissues, such as serum, in addition to primary tissues and so may have advantages over genetic biomarkers. Glutathione S -transferase pi 1 ( GSTP1 ) is the best-studied example of an epigenetic biomarker for cancer diagnosis. However, additional candidates show a high potential for future clinical applications, although specificity of diagnosis is an issue, and combinatorial approaches analysing DNA methylation alterations at several genes may improve this. Single-gene approaches have identified epigenetic biomarkers that predict cancer recurrence and survival. Recently, high-resolution genome-wide technologies have shown the potential to improve this strategy with DNA methylation signatures of cancers showing high predictive capacity of disease prognosis. DNA methylation alterations may be used as biomarkers to predict response to chemotherapy strategies. O 6 -methylguanine DNA methyltransferase ( MGMT ) and breast cancer 1, early onset ( BRCA1 ) are examples of hypermethylated genes that predict a response to chemotherapy in cancer. Additional prognostic gene markers have already been identified and suggest DNA methylation profiling as a potent strategy to predict drug response. Recent advances in sequencing and array technologies, which are capable of screening DNA methylomes genome-wide at high-resolution, gave unexpected novel insights in cancer biology. They will be crucial for DNA methylation profiling and the identification of epigenetic biomarker for diagnosis, prognosis and prediction of drug response. Epigenetic alterations, notably in DNA hypermethylation, are emerging as consistent biomarkers for disease. Here, with a focus on cancer, the authors discuss the identification of these biomarkers and their use in disease diagnosis, prognosis and response to therapy. Knowledge of epigenetic alterations in disease is rapidly increasing owing to the development of genome-wide techniques for their identification. The ever-growing number of genes that show epigenetic alterations in disease emphasizes the crucial role of these epigenetic alterations — particularly DNA methylation — for future diagnosis, prognosis and prediction of response to therapies. This Review focuses on epigenetic profiling, which has started to be of clinical value in cancer and may in the future be extended to other diseases, such as neurological and autoimmune disorders.
Audience	Academic
Author	Esteller, Manel Heyn, Holger
Author_xml	– sequence: 1 givenname: Holger surname: Heyn fullname: Heyn, Holger organization: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL) – sequence: 2 givenname: Manel surname: Esteller fullname: Esteller, Manel email: mesteller@idibell.cat organization: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Department of Physiological Sciences II, School of Medicine, University of Barcelona, Instituci Catalana de Recerca i Estudis Avançats (ICREA)
BackLink	http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26355350$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/22945394$$D View this record in MEDLINE/PubMed
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Snippet	Key Points Alterations in epigenetic marks — specifically DNA methylation — are an emerging biomarker that may be used in the decision-making process for... Knowledge of epigenetic alterations in disease is rapidly increasing owing to the development of genome-wide techniques for their identification. The...
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SubjectTerms	631/208/176/1988 631/208/191/2018 631/208/721 Agriculture Animal Genetics and Genomics Animals Biological and medical sciences Biomarkers Biomedical and Life Sciences Biomedicine Cancer Research Clinical Laboratory Techniques - methods Clinical Laboratory Techniques - standards Datasets Disease Disease - genetics DNA DNA methylation DNA Methylation - physiology Epigenesis, Genetic - physiology Epigenetic inheritance Epigenetics Fundamental and applied biological sciences. Psychology Gene Expression Profiling - methods Gene Expression Profiling - statistics & numerical data Gene Function Genes Genetic aspects Genetics of eukaryotes. Biological and molecular evolution Genomes Health aspects Human Genetics Humans Medical diagnosis Methylation Models, Biological Molecular Targeted Therapy - methods Molecular Targeted Therapy - trends Mutation Prostate cancer review-article
Title	DNA methylation profiling in the clinic: applications and challenges
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