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Series GSE60185 Query DataSets for GSE60185
Status Public on Aug 08, 2014
Title Genome-wide DNA methylation profiles in progression to in situ and invasive carcinoma of the breast with impact on gene transcription and prognosis
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary Ductal carcinoma in situ (DCIS) of the breast is a precursor of invasive breast carcinoma (IBC). DNA methylation alterations are thought to be an early event in progression of cancer, and may prove valuable as a tool in clinical decision making and for understanding neoplastic development. Genome-wide DNA methylation profiles of 285 breast tissue samples representing progression of cancer were generated using Illumina HumanMethylation450. Validation of methylation changes between normal and DCIS was performed in an independent dataset of 15 normal and 40 DCIS samples, and validation of a prognostic signature was performed on 583 breast cancer samples from The Cancer Genome Atlas. Using two independent datasets of normal breast tissue and DCIS revealed that DNA methylation profiles of DCIS were radically altered compared to normal breast tissue, involving almost 7000 genes (including CUL7 and ICAM2). Changes between DCIS and IBC involved around 1000 genes. In tumors, DNA methylation was associated with gene expression of almost 3000 genes (p<0.05, Bonferroni corrected) including both negative and positive correlations. A prognostic signature based on methylation level of 18 CpGs (representing genes such as IRF6, TBX5, ZNF259, KCTD21, EPN3, MACF1 and CSNK1G2) was associated to survival of breast cancer patients with invasive tumors, as well as to survival of patients with DCIS and mixed lesions of DCIS and IBC. This work demonstrates that changes in the epigenome occurs early in the neoplastic progression, provide evidence for the possible utilization of DNA methylation based markers of progression in the clinic, and highlights the importance of epigenetic changes in carcinogenesis.
Overall design Bisulphite converted DNA from the 285 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
Contributor(s) Fleischer T, Frigessi A, Johnson KC, Edvardsen H, Touleimat N, Klajic J, Riis ML, Haakensen VD, Wärnberg F, Naume B, Helland Å, Børresen-Dale A, Tost J, Christensen BC, Kristensen VN
Citation(s) 25146004, 21364938, 35350772
Submission date Aug 07, 2014
Last update date Apr 06, 2022
Contact name Thomas Fleischer
Organization name Oslo University Hospital
Department Department of Cancer Genetics, Institute for Cancer Research
Street address Ullernchausséen 70
City Oslo
ZIP/Postal code 0310
Country Norway
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (285)
GSM1466940 GS0005740
GSM1466941 GS0005599
GSM1466942 GS0005604
BioProject PRJNA257696

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE60185_RAW.tar 2.5 Gb (http)(custom) TAR (of IDAT)
Processed data included within Sample table

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