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E-GEOD-40105 - The DNA methylomes of serous borderline tumours reveal subgroups with malignant-like or benign-like profiles

Status
Released on 31 December 2012, last updated on 2 June 2014
Organism
Homo sapiens
Samples (51)
Array (1)
Protocols (6)
Description
Serous borderline tumours (SBOT) are a challenging group of ovarian tumours positioned between benign and malignant disease. We have profiled the DNA methylomes of 12 low grade serous carcinoma (LGSC), 19 SBOT and 16 benign serous tumours (BST) across 27,578 CpG sites to further characterise the epigenomic relationship between these subtypes of ovarian tumours. Unsupervised hierarchical clustering of DNA methylation levels showed that LGSC differ distinctly from BST, however, not from SBOT. Gene ontology analysis of genes showing differential methylation at linked CpG sites between LGSC and BST revealed significant enrichment of gene groups associated with cell adhesion, cell-cell signalling and the extracellular region consistent with a more invasive phenotype of LGSC as compared to BST. Consensus clustering highlighted differences between SBOT methylomes and returned subgroups with malignant-like or benign-like methylation profiles. Furthermore, a two loci DNA methylation signature can distinguish between these SBOT subgroups with benign-like and malignant-like methylation characteristics. Our findings indicate striking similarities between SBOT and LGSC methylomes which supports a common origin and the view that LGSC may arise from SBOT. A subgroup of SBOT can be classified into tumours with a benign-like or a malignant-like methylation profile which may help in identifying tumours more likely to progress into LGSC. Array-based methylation profiling was performed using the Infinium HumanMethylation27 BeadChip in 12 low grade serous carcinoma, 19 serous borderline tumours and 16 benign serous tumours. The reproducibility of the Infinium HumanMethylation27 BeadChips was evaluated using four biological replicates of the high grade serous ovarian cancer cell line PEO1. Differential methylation cutoff was estimated from four biological replicates by bootstrap resampling and set at Δβ ≥ 0.25 corresponding to a FDR ≤ 0.09.
Experiment type
methylation profiling by array 
Contacts
Afshan Siddiq, Andrew Walley, Constanze Zeller, Edward Curry, Gail Anderson, Isidora Kitsou-Mylona, Mona El-Bahrawy, Nahal Masrour, Robert Brown, Sadaf Ghaem-Maghami, Wei Dai
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-40105.idf.txt
Sample and data relationshipE-GEOD-40105.sdrf.txt
Processed data (1)E-GEOD-40105.processed.1.zip
Additional data (1)E-GEOD-40105.additional.1.zip
Array designA-GEOD-8490.adf.txt
Links