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A Panel of Differentially Methylated Putative Imprinting Control Regions Associated with Hepatocellular Carcinoma

Listed in NCBI GEO

Site-specific 5-methylcytosine levels measured in mixed blood leukocytes have been used as surrogate for inaccessible tissues and associated with hepatocellular carcinoma (HCC) risk.

Description

However, findings are difficult to replicate as methylation patterns at many of these sites do not always correlate with those in liver tissue. An exception is methylation at imprinting control regions (ICRs), which regulate the monoallelic expression of imprinted genes, a developmentally critical process requiring parental allele-specific DNA methylation that is consistent across cell types.

Aberrant methylation of several ICRs have been linked to advanced liver disease or HCC. We aim to create a DNA methylation-based risk stratification panel to improve early detection and triaging of patients before the onset of HCC in those at increased risk. From whole genome bisulfite sequencing (WGBS) of mixed leukocyte-derived DNA of HCC cases and controls, 1,519 regions were significantly differentially methylated.

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This list was augmented with a compendium of 3,275 HCC-, cirrhosis-, and fibrosis-associated differentially methylated regions (DMRs) identified from primary literature on PubMed, for a total of 4794 unique DMRs. Filtering these DMRs with a published list of ICRs revealed 97 ICRs within these liver disease-associated DMRs, 21 of them previously characterized and 76 novel. Of these ICRs, 46 replicated in an independent case-control comparison using the novel Illumina custom Imprintome Methylation array.

Limited sample sizes notwithstanding, this comprehensive analysis supports the use of altered DNA methylation of ICRs for HCC risk stratification from readily accessible tissue, blood.

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Topics

From keywords
Life Sciences
Inferred from text
Disease 75% · DNA methylation profiling 65% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE30260812 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:diseaseenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:methylation-profiling-by-arraysource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[method].local:method:dna-methylation-profilingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title