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CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer
- D. Weisenberger, K. Siegmund, P. Laird
- BiologyNature Genetics
- 1 July 2006
A systematic, stepwise screen of 195 CpG island methylation markers using MethyLight technology found that CIMP-positive (CIMP+) tumors convincingly represent a distinct subset, encompassing almost all cases of tumors with BRAFmutation (odds ratio = 203).
Epigenetic stem cell signature in cancer
- M. Widschwendter, H. Fiegl, P. Laird
- BiologyNature Genetics
- 1 February 2007
It is reported that stem cell Polycomb group targets are up to 12-fold more likely to have cancer-specific promoter DNA hypermethylation than non-targets, supporting a stem cell origin of cancer in which reversible gene repression is replaced by permanent silencing, locking the cell into a perpetual state of self-renewal and thereby predisposing to subsequent malignant transformation.
Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer.
- A. Teschendorff, U. Menon, M. Widschwendter
- BiologyGenome Research
- 1 April 2010
It is found that the age-PCGT methylation signature is present in preneoplastic conditions and may drive gene expression changes associated with carcinogenesis in normal and cancer solid tissues and a population of bone marrow mesenchymal stem/stromal cells.
Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer
- D. Schramek, A. Leibbrandt, J. Penninger
- Biology, MedicineNature
- 4 November 2010
It is shown that the in vivo administration of MPA triggers massive induction of the key osteoclast differentiation factor RANKL (receptor activator of NF-κB ligand) in mammary-gland epithelial cells and controls the incidence and onset of progestin-driven breast cancer.
FBXW7/hCDC4 is a general tumor suppressor in human cancer.
- Shahab Akhoondi, Dahui Sun, C. Spruck
- BiologyCancer Research
- 1 October 2007
This study is the first comprehensive screen of FBXW7 mutations in various human malignancies and shows that FBxW7 is a general tumor suppressor in human cancer.
Methylation and silencing of the retinoic acid receptor-beta2 gene in breast cancer.
- M. Widschwendter, J. Berger, C. Marth
- Medicine, BiologyJournal of the National Cancer Institute
- 17 May 2000
Methylation of the RAR-beta2 gene may be an initial step in breast carcinogenesis; treatment of cancer patients with demethylating agents followed by retinoic acid may offer a new therapeutic modality.
DNA methylation and breast carcinogenesis
- M. Widschwendter, Peter A. Jones
- BiologyOncogene
- 12 August 2002
How DNA-methylation contributes to breast cancer features and suggestions about how these changes could be prevented, reverted or used as a ‘tag’ for early detection of breast cancer or, preferably, for detection of premalignant changes are offered.
Association of Breast Cancer DNA Methylation Profiles with Hormone Receptor Status and Response to Tamoxifen
- M. Widschwendter, K. Siegmund, P. Laird
- Biology, MedicineCancer Research
- 1 June 2004
The results reveal an as yet unrecognized degree of interaction between DNA methylation and HR biology in breast cancer cells and suggest potentially clinically useful novel DNAmethylation predictors of response to hormonal and non-hormonal breast cancer therapy.
Independent surrogate variable analysis to deconvolve confounding factors in large-scale microarray profiling studies
- A. Teschendorff, Joanna Zhuang, M. Widschwendter
- Computer ScienceBioinform.
- 1 June 2011
Using four large-scale Illumina Infinium DNA methylation datasets subject to low signal to noise ratios and substantial confounding by beadchip effects and variable bisulfite conversion efficiency, ISVA improves the identifiability of confounders and enables a framework for feature selection that is more robust to model misspecification and heterogeneous phenotypes.
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