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| Status |
Public on Jun 01, 2015 |
| Title |
DNA methylation in ductal carcinoma in situ related with future development of invasive breast cancer |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
|
| Summary |
Ductal carcinoma in situ (DCIS) is a heterogeneous, pre-invasive lesion associated with an increased risk for future invasive ductal carcinoma. However, accurate risk stratification for development of invasive disease and appropriate treatment decisions remain clinical challenges. DNA methylation alterations are recognized to be early events in the progression of cancer and represent emerging molecular markers that may predict invasive recurrence more accurately than traditional measures of DCIS prognosis. We measured DNA methylation of DCIS (n=40) and adjacent normal (n=15) tissues using the Illumina HumanMethylation450 array. We identified locus-specific methylation differences between DCIS and matched adjacent-normal tissue (95,609 CpGs, Q < 0.05). Among 40 DCIS cases 13 later developed invasive disease and we identified 641 CpG sites that exhibited differential DNA methylation (P < 0.01 and medianúΔβú > 0.1) in these cases compared with age-matched subjects without invasive disease over a similar follow up period. The set of differentially methylated CpG loci associated with disease progression was enriched in homeobox-containing genes (P = 1.3E-9) and genes involved with limb morphogenesis (P = 1.0E-05). In an independent cohort, a subset of genes with progression-related differential methylation between DCIS and invasive breast cancer were confirmed. Further, the functional relevance of these genes’ regulation by methylation was demonstrated in early stage breast cancers from The Cancer Genome Atlas database. This work contributes to the understanding of epigenetic alterations that occur in DCIS and illustrates the potential of DNA methylation as markers of DCIS progression.
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| Overall design |
Bisulfite converted DNA from the 55 samples (40 DCIS and 15 adjacent-normal) that were hybridized to the Illumina Infinium 450K Human Methylation beadchip
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| Contributor(s) |
Johnson KC |
| Citation(s) |
26213588, 28711544, 31842685 |
| Submission date |
Feb 25, 2015 |
| Last update date |
Apr 20, 2020 |
| Contact name |
Kevin Crowley Johnson |
| E-mail(s) |
Kevin.c.johnson.gr@dartmouth.edu
|
| Organization name |
Geisel School of Medicine at Dartmouth College
|
| Department |
Epidemiology
|
| Lab |
Christensen Lab
|
| Street address |
72 College Street
|
| City |
Hanover |
| State/province |
NH |
| ZIP/Postal code |
03755 |
| Country |
USA |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (55)
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| Relations |
| BioProject |
PRJNA276485 |
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