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Cancer diagnostic classifiers based on quantitative DNA methylation.

Lorincz AT - Expert Rev. Mol. Diagn. (2014)

Bottom Line: Differential methylation may have a central role in the development and outcome of most if not all human malignancies.The advent of deep sequencing holds great promise for epigenomics, with bioinformatics tools ready to reveal large numbers of new targets for prognosis and therapeutic intervention.Also discussed is differential methylation of specific human and viral DNA targets and laboratory methods for measuring methylation biomarkers.

View Article: PubMed Central - PubMed

Affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, EC1M 6BQ, UK.

ABSTRACT
Epigenetic change is part of the carcinogenic process and a deep reservoir for biomarker discovery. Reversible methylation of cytosines is noteworthy because it can be measured accurately and easily by various molecular methods and DNA methylation patterns are linked to important tumourigenic pathways. Clinically relevant methylation changes are known in common human cancers such as cervix, prostate, breast, colon, bladder, stomach and lung. Differential methylation may have a central role in the development and outcome of most if not all human malignancies. The advent of deep sequencing holds great promise for epigenomics, with bioinformatics tools ready to reveal large numbers of new targets for prognosis and therapeutic intervention. This review focuses on two selected cancers, namely cervix and prostate, which illustrate the more general themes of epigenetic diagnostics in cancer. Also discussed is differential methylation of specific human and viral DNA targets and laboratory methods for measuring methylation biomarkers.

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Related in: MedlinePlus

DNA methylation patterns across the genome of HPV16, showing the percentage median values for selected CpG sites in cancers (solid circles), cervical intraepthelial neoplasia 2/3 (triangles), and normal women who had transient HPV16 infections (open circles). Other hrHPVs have similar methylation patterns, with relative peaks in the L1 and L2 regions and little to no methylation in the URR. The circular genome is depicted as opened in the URR region. The specific peaks and valleys of the HPV16 genome methylation profile are quite reproducible in specimens from different geographic locations and may reflect the intrinsic relative positions of histones and other binding complexes.
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Figure 2: DNA methylation patterns across the genome of HPV16, showing the percentage median values for selected CpG sites in cancers (solid circles), cervical intraepthelial neoplasia 2/3 (triangles), and normal women who had transient HPV16 infections (open circles). Other hrHPVs have similar methylation patterns, with relative peaks in the L1 and L2 regions and little to no methylation in the URR. The circular genome is depicted as opened in the URR region. The specific peaks and valleys of the HPV16 genome methylation profile are quite reproducible in specimens from different geographic locations and may reflect the intrinsic relative positions of histones and other binding complexes.

Mentions: A number of other hrHPVs have been investigated for methylation, including HPV18, HPV31, HPV33, HPV45, HPV52 and HPV58. These types have been studied to a lesser extent than HPV16 and there are no methylation data available on many hrHPV types [33,37,38]. The methylation patterns of investigated hrHPV genomes are quite similar. Methylation levels are low or absent in the URR and E6 regions in women with normal cytology but there is a gradual increase through E7, E1 and E2 to reach peak values in the L2 and L1 regions (Figure 2). This pattern is also mostly maintained in CIN lesions through to cancer, although the slopes become steeper and the peaks become higher with increasing disease severity. Average methylation values in the L1 region in normal tissues is in the range of 5–10%, while in cancer, the values are typically 40–80% (Figure 2)[10].


Cancer diagnostic classifiers based on quantitative DNA methylation.

Lorincz AT - Expert Rev. Mol. Diagn. (2014)

DNA methylation patterns across the genome of HPV16, showing the percentage median values for selected CpG sites in cancers (solid circles), cervical intraepthelial neoplasia 2/3 (triangles), and normal women who had transient HPV16 infections (open circles). Other hrHPVs have similar methylation patterns, with relative peaks in the L1 and L2 regions and little to no methylation in the URR. The circular genome is depicted as opened in the URR region. The specific peaks and valleys of the HPV16 genome methylation profile are quite reproducible in specimens from different geographic locations and may reflect the intrinsic relative positions of histones and other binding complexes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4225655&req=5

Figure 2: DNA methylation patterns across the genome of HPV16, showing the percentage median values for selected CpG sites in cancers (solid circles), cervical intraepthelial neoplasia 2/3 (triangles), and normal women who had transient HPV16 infections (open circles). Other hrHPVs have similar methylation patterns, with relative peaks in the L1 and L2 regions and little to no methylation in the URR. The circular genome is depicted as opened in the URR region. The specific peaks and valleys of the HPV16 genome methylation profile are quite reproducible in specimens from different geographic locations and may reflect the intrinsic relative positions of histones and other binding complexes.
Mentions: A number of other hrHPVs have been investigated for methylation, including HPV18, HPV31, HPV33, HPV45, HPV52 and HPV58. These types have been studied to a lesser extent than HPV16 and there are no methylation data available on many hrHPV types [33,37,38]. The methylation patterns of investigated hrHPV genomes are quite similar. Methylation levels are low or absent in the URR and E6 regions in women with normal cytology but there is a gradual increase through E7, E1 and E2 to reach peak values in the L2 and L1 regions (Figure 2). This pattern is also mostly maintained in CIN lesions through to cancer, although the slopes become steeper and the peaks become higher with increasing disease severity. Average methylation values in the L1 region in normal tissues is in the range of 5–10%, while in cancer, the values are typically 40–80% (Figure 2)[10].

Bottom Line: Differential methylation may have a central role in the development and outcome of most if not all human malignancies.The advent of deep sequencing holds great promise for epigenomics, with bioinformatics tools ready to reveal large numbers of new targets for prognosis and therapeutic intervention.Also discussed is differential methylation of specific human and viral DNA targets and laboratory methods for measuring methylation biomarkers.

View Article: PubMed Central - PubMed

Affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, EC1M 6BQ, UK.

ABSTRACT
Epigenetic change is part of the carcinogenic process and a deep reservoir for biomarker discovery. Reversible methylation of cytosines is noteworthy because it can be measured accurately and easily by various molecular methods and DNA methylation patterns are linked to important tumourigenic pathways. Clinically relevant methylation changes are known in common human cancers such as cervix, prostate, breast, colon, bladder, stomach and lung. Differential methylation may have a central role in the development and outcome of most if not all human malignancies. The advent of deep sequencing holds great promise for epigenomics, with bioinformatics tools ready to reveal large numbers of new targets for prognosis and therapeutic intervention. This review focuses on two selected cancers, namely cervix and prostate, which illustrate the more general themes of epigenetic diagnostics in cancer. Also discussed is differential methylation of specific human and viral DNA targets and laboratory methods for measuring methylation biomarkers.

Show MeSH
Related in: MedlinePlus