All Things in Moderation: Prevention of Intestinal Adenomas by DNA Hypomethylation.
Cancer Prevention Research 9(7):509 (2016)
DNA hypomethylation can prevent intestinal tumorigenesis, presumably by reducing epigenetic silencing of tumor-suppressor genes. A study in this issue by Sheaffer and colleagues challenges this notion by showing that severe DNA hypomethylation by tissue-specific Dnmt1 knockout can actually promo...
Effects of folylpolyglutamate synthase modulation on global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells.
The Journal of Nutritional Biochemistry 29:27 (2016)
Folylpolyglutamate synthase (FPGS) plays a critical role in intracellular folate homeostasis. FPGS-induced polyglutamylated folates are better substrates for several enzymes involved in the generation of S-adenosylmethionine, the primary methyl group donor, and hence FPGS modulation may affect D...
Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma.
Cell 164(3):550 (2016)
Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular...
Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.
New England Journal of Medicine 374(2):135 (2016)
Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is kno...
Promoter Methylation Analysis Reveals That KCNA5 Ion Channel Silencing Supports Ewing Sarcoma Cell Proliferation.
Molecular Cancer Research 14(1):26 (2016)
Polycomb proteins are essential regulators of gene expression in stem cells and development. They function to reversibly repress gene transcription via posttranslational modification of histones and chromatin compaction. In many human cancers, genes that are repressed by polycomb in stem cells a...
Clinicopathologic Risk Factor Distributions for MLH1 Promoter Region Methylation in CIMP-Positive Tumors.
Cancer Epidemiology Biomarkers & Prevention 25(1):68 (2016)
The CpG island methylator phenotype (CIMP) is a major molecular pathway in colorectal cancer. Approximately 25% to 60% of CIMP tumors are microsatellite unstable (MSI-H) due to DNA hypermethylation of the MLH1 gene promoter. Our aim was to determine if the distributions of clinicopathologic fact...
Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.
Cell 163(2):506 (2015)
Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified ...
Tumor Budding in Colorectal Carcinoma: Confirmation of Prognostic Significance and Histologic Cutoff in a Population-based Cohort.
The American Journal of Surgical Pathology 39(10):1340 (2015)
Tumor budding in colorectal carcinoma has been associated with poor outcome in multiple studies, but the absence of an established histologic cutoff for "high" tumor budding, heterogeneity in study populations, and varying methods for assessing tumor budding have hindered widespread incorporatio...
Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.
New England Journal of Medicine 372(26):2481 (2015)
Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to g...
Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution.
Genome Research 25(3):316 (2015)
Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence ∼ 7 mo after diagnosis. Understanding the molecular architecture of this res...
Association of the colorectal CpG island methylator phenotype with molecular features, risk factors, and family history.
Cancer Epidemiology Biomarkers & Prevention 24(3):512 (2015)
The CpG island methylator phenotype (CIMP) represents a subset of colorectal cancers characterized by widespread aberrant DNA hypermethylation at select CpG islands. The risk factors and environmental exposures contributing to etiologic heterogeneity between CIMP and non-CIMP tumors are not know...
Association between molecular subtypes of colorectal cancer and patient survival.
Gastroenterology 148(1):77 (2015)
Colorectal cancer (CRC) is a heterogeneous disease that can develop via several pathways. Different CRC subtypes, identified based on tumor markers, have been proposed to reflect these pathways. We evaluated the significance of these previously proposed classifications to survival.
Inferring regulatory element landscapes and transcription factor networks from cancer methylomes.
Genome Biology 16(1):105 (2015)
Recent studies indicate that DNA methylation can be used to identify transcriptional enhancers, but no systematic approach has been developed for genome-wide identification and analysis of enhancers based on DNA methylation. We describe ELMER (Enhancer Linking by Methylation/Expression Relations...
γ-Glutamyl hydrolase modulation significantly influences global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells.
Genes & Nutrition 10(1):444 (2015)
γ-Glutamyl hydrolase (GGH) plays an important role in folate homeostasis by catalyzing hydrolysis of polyglutamylated folate into monoglutamates. Polyglutamylated folates are better substrates for several enzymes involved in the generation of S-adenosylmethionine, the primary methyl group donor,...
The somatic genomic landscape of chromophobe renal cell carcinoma.
Cancer Cell 26(3):319 (2014)
We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compa...
Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin.
Cell 158(4):929 (2014)
Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform ...
Multiscale representation of genomic signals.
Nature Methods 11(6):689 (2014)
Genomic information is encoded on a wide range of distance scales, ranging from tens of bases to megabases. We developed a multiscale framework to analyze and visualize the information content of genomic signals. Different types of signals, such as G+C content or DNA methylation, are characteriz...
Abstract 31: DNA methylation analysis of radiated skin reveals chonic inflammation with a predominance of polymorphonuclear granulocytes.
Plastic & Reconstructive Surgery 133(3 Suppl):42 (2014)
Non-specific filtering of beta-distributed data.
BMC Bioinformatics 15:199 (2014)
Non-specific feature selection is a dimension reduction procedure performed prior to cluster analysis of high dimensional molecular data. Not all measured features are expected to show biological variation, so only the most varying are selected for analysis. In DNA methylation studies, DNA methy...
An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma.
JNCI Journal of the National Cancer Institute 105(24):1862 (2013)
Obesity increases risk for clear-cell renal cell carcinoma (ccRCC), yet obese patients appear to experience longer survival than nonobese patients. We examined body mass index (BMI) in relation to stage, grade, and cancer-specific mortality (CSM) while considering detection bias, nutritional sta...