Andrew E Teschendorff

..Reliable identification of ER-negative tumors that have a good prognosis is not yet possible...

..To date, most genome-wide array comparative genomic hybridization studies have used tumor panels of relatively large tumor size and high Nottingham Prognostic Index (NPI) that are not as representative of breast cancer demographics...

..However, identification of such patients with a good prognosis remains difficult and at present is only possible through examining histopathological factors...

..we address the following issues: Do these signatures perform similarly? Are there (common) molecular processes reported by these signatures? Can better prognostic predictors be constructed based on these identified molecular processes?..

..We assessed a modified method, in which external calibration curves were generated from a single construct containing HPV16 E2, HPV16 E6 and the host gene hydroxymethylbilane synthase in a 1:1:1 ratio...

..We also compare the two criteria using freely available tumour microarray datasets and show that the variational Bayesian method is more sensitive to capturing biologically relevant structure...

....

..Adopting ICA as the analysis tool of choice will help understand the phenotype-pathway relationship and thus help elucidate the molecular taxonomy of heterogeneous cancers and of other complex genetic diseases...

..A consensus prognostic gene expression classifier is still elusive in heterogeneous diseases such as breast cancer...

..Feature selection methods that can identify relevant classifiers or that can remove likely false positives prior to supervised analysis are therefore desirable...

....

..Cases had T1D and nephropathy whereas controls had T1D but no evidence of renal disease...

..These findings shed substantial novel insights into the epigenetic effects of aging and support the view that age may predispose to malignant transformation by irreversibly stabilizing stem cell features...

..These data suggest that a NGF/BEX2/NF-kappaB pathway is involved in regulating apoptosis in breast cancer cells and in modulating response to tamoxifen in primary tumors...

..This study establishes MeDIP-seq as an effective method to analyze cancer methylomes...

..These results suggest that COMT rs4818, or a variant it tags, is associated with breast cancer prognosis. Further study of COMT and its putative association with breast cancer prognosis is warranted...

..We propose a model in which the Oct-1/Runx2 and C/EBPbeta binding sites in the disease-associated allele are able to lead to an increase in FGFR2 gene expression, thereby increasing the propensity for tumour formation...

..MicroRNAs (miRNAs), a class of short non-coding RNAs found in many plants and animals, often act post-transcriptionally to inhibit gene expression...

..By establishing transcription-factor mapping in primary tumour material, we show that there is plasticity in ER-binding capacity, with distinct combinations of cis-regulatory elements linked with the different clinical outcomes...

..However, relatively few strategies for estimating pathway activity from such model signatures exist and only few studies have used activation patterns of pathways to refine molecular classifications of cancer...

..However, relatively little is known as to what network features differ between the cancer and normal cell physiologies, or between different cancer cell phenotypes...

..We envisage that further improvements and insights may come from integrative expression pathway analyses that dissect prognostic signatures into modules related to cancer hallmarks...

..To deal with these difficulties, an algorithmic framework known as Surrogate Variable Analysis (SVA) was recently proposed...

..This article contains supplementary material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat...

..Expression of each gene in 225 samples (135 primary tumours, 47 cancer cell lines, and 43 normal tissues) was analysedby QRT-PCR, normalized with 8 housekeeping genes, and given as a ratio by comparison with a universal reference RNA...

..Of particular interest are genes involved in cell cycle pathways, which regulate cell division...

..However, to date no study has evaluated the diagnostic and predictive potential of such markers in a large case control cohort and on a genome-wide basis...

..These findings have major implications for cancer and embryonic stem cell biology and establish the importance of systemic DNA hypomethylation for predicting prognosis in a wide range of different cancers...

..We show that the latter is predicted by a simple model that invokes random breakage following anchorage of some random point on the chromosome, or selection of breaks proximal to one of several tumor suppressor genes...

..Greater emphasis should be placed on episome loss in models of HPV-related carcinogenesis. We provide the strongest evidence to date that treating HPV-16 lesions by inducing an IFN response may cause clinical progression...

..abstract:..