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| 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
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| 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.
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| Overall design |
Bisulphite converted DNA from the 285 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
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| 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 |
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| Submission date |
Aug 07, 2014 |
| Last update date |
Apr 06, 2022 |
| Contact name |
Thomas Fleischer |
| E-mail(s) |
thomas.fleischer@rr-research.no
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| Organization name |
Oslo University Hospital
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| Department |
Department of Cancer Genetics, Institute for Cancer Research
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| Street address |
Ullernchausséen 70
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| City |
Oslo |
| ZIP/Postal code |
0310 |
| Country |
Norway |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (285)
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| Relations |
| BioProject |
PRJNA257696 |
| 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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