Novel DNA Methylation Biomarker Panel for Detection of Esophageal Adenocarcinoma and High-Grade Dysplasia.

Purpose: Current endoscopy-based screening and surveillance programs have not been proven effective at decreasing esophageal adenocarcinoma (EAC) mortality, creating an unmet need for effective molecular tests for early detection of this highly lethal cancer. We conducted a genome-wide methylation screen to identify novel methylation markers that distinguish EAC and high-grade dysplasia (HGD) from normal squamous epithelium (SQ) or nondysplastic Barrett's esophagus (NDBE).

Experimental Design: DNA methylation profiling of samples from SQ, NDBE, HGD, and EAC was performed using HM450 methylation arrays (Illumina) and reduced-representation bisulfate sequencing.

Epigenetic Inactivation of α-Internexin Accelerates Microtubule Polymerization in Colorectal Cancer.

DNA methylation contributes to malignant transformation, but little is known about how the methylation drives colorectal cancer evolution at the early stages. Here we identify aberrant INA (α-internexin) gene methylation in colon adenoma and adenocarcinoma by filtering data obtained from a genome-wide screen of methylated genes. The gene encoding INA, a type IV intermediate filament, was frequently hypermethylated in CpG islands located in the promoter region.

Chemoprevention of esophageal adenocarcinoma.

Esophageal adenocarcinoma (EAC) is a major cause of cancer-related death, particularly in Western populations, and is rapidly rising in Asian populations at this time. Virtually all EACs develop from the precursor lesion Barrett's esophagus (BE), which is the most significant risk factor for EAC. However, the rates of progression from BE to EAC are low and patients with BE are asymptomatic.

Colonic mucosal and exfoliome transcriptomic profiling and fecal microbiome response to a flaxseed lignan extract intervention in humans.

Background: Microbial metabolism of lignans from high-fiber plant foods produces bioactive enterolignans, such as enterolactone (ENL) and enterodiol (END). Enterolignan exposure influences cellular pathways important to cancer risk and is associated with reduced colon tumorigenesis in animal models and lower colorectal cancer risk in humans.

Objectives: The aim of this study was to test the effects of a flaxseed lignan supplement (50 mg secoisolariciresinol diglucoside/d) compared with placebo on host gene expression in colon biopsies and exfoliated colonocyte RNA in feces and fecal microbial community composition, and to compare responses in relation to ENL excretion.

Implications of Epigenetic Drift in Colorectal Neoplasia.

Many normal tissues undergo age-related drift in DNA methylation, providing a quantitative measure of tissue age. Here, we identify and validate 781 CpG islands (CGI) that undergo significant methylomic drift in 232 normal colorectal tissues and show that these CGI continue to drift in neoplasia while retaining significant correlations across samples. However, compared with normal colon, this drift advanced (∼3-4-fold) faster in neoplasia, consistent with increased cell proliferation during neoplastic progression.

Subtypes of Barrett's oesophagus and oesophageal adenocarcinoma based on genome-wide methylation analysis.

Objective: To identify and characterise DNA methylation subtypes in oesophageal adenocarcinoma (EAC) and its precursor Barrett's oesophagus (BE).

Design: We performed genome-wide DNA methylation profiling on samples of non-dysplastic BE from cancer-free patients (n=59), EAC (n=23), normal squamous oesophagus (n=33) and normal fundus (n=9), and identified methylation subtypes using a recursively partitioned mixture model. We assessed genomic alterations for 9 BE and 22 EAC samples with massively parallel sequencing of 243 EAC-associated genes, and we conducted integrative analyses with transcriptome data to identify epigenetically repressed genes.

Editorial: The Name Game: Circumventing Quality Metrics by Categorizing Incomplete Colonoscopy as Sigmoidoscopy.

Cecal intubation rate (CIR) is an important metric for colonoscopy quality. Guidelines propose a minimum CIR of 90% for all indications, and 95% in screening procedures. In this issue, a study of three UK teaching hospitals demonstrated one-third of endoscopists inappropriately converted colonoscopies to flexible sigmoidoscopies, and several endoscopists only reached the 90% CIR benchmark because of these inappropriate conversions.

BVES regulates c-Myc stability via PP2A and suppresses colitis-induced tumourigenesis.

Objective: Blood vessel epicardial substance (BVES) is a tight junction-associated protein that regulates epithelial-mesenchymal states and is underexpressed in epithelial malignancy. However, the functional impact of BVES loss on tumourigenesis is unknown. Here we define the in vivo role of BVES in colitis-associated cancer (CAC), its cellular function and its relevance to patients with IBD.

Erratum to: Global DNA methylation patterns in Barrett's esophagus, dysplastic Barrett's, and esophageal adenocarcinoma are associated with BMI, gender, and tobacco use.

[This corrects the article DOI: 10.1186/s13148-016-0273-7.].

Anal intraepithelial neoplasia: A review of diagnosis and management.

Anal intraepithelial neoplasia (AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus (HPV) infection.

Global DNA methylation patterns in Barrett's esophagus, dysplastic Barrett's, and esophageal adenocarcinoma are associated with BMI, gender, and tobacco use.

Background: The risk of developing Barrett's esophagus (BE) and/or esophageal adenocarcinoma (EAC) is associated with specific demographic and behavioral factors, including gender, obesity/elevated body mass index (BMI), and tobacco use. Alterations in DNA methylation, an epigenetic modification that can affect gene expression and that can be influenced by environmental factors, is frequently present in both BE and EAC and is believed to play a role in the formation of BE and its progression to EAC. It is currently unknown whether obesity or tobacco smoking influences the risk of developing BE/EAC via the induction of alterations in DNA methylation.

Epigenetic silencing of TPM2 contributes to colorectal cancer progression upon RhoA activation.

Beta-tropomyosin (β-tropomyosin, TPM2) has been found to be downregulated in colorectal cancer (CRC) in previous studies. In this study, we aimed to investigate the mechanisms and potential biological consequences of the downregulation of TPM2 in colorectal cancer. TPM2 expression in colorectal cancer was assessed by qRT-PCR and immunostaining.

Comprehensive site-specific whole genome profiling of stromal and epithelial colonic gene signatures in human sigmoid colon and rectal tissue.

The strength of associations between various exposures (e.g., diet, tobacco, chemopreventive agents) and colorectal cancer risk may partially depend on the complex interaction between epithelium and stroma across anatomic subsites.

A Molecular Clock Infers Heterogeneous Tissue Age Among Patients with Barrett's Esophagus.

Biomarkers that drift differentially with age between normal and premalignant tissues, such as Barrett's esophagus (BE), have the potential to improve the assessment of a patient's cancer risk by providing quantitative information about how long a patient has lived with the precursor (i.e., dwell time).

Universal Screening of Colorectal Cancers for Lynch Syndrome: Challenges and Opportunities.

Lynch syndrome (LS) is the most common heritable colorectal cancer (CRC) syndrome, accounting for approximately 3 % of CRC cases in the USA each year. LS results from a genetic mutation in one of the four mismatch repair genes, and clinically LS is associated with CRC and other gastrointestinal and extra-gastrointestinal malignancies. In this review, we describe the various clinical criteria utilized for the identification of LS patients and the inherent flaws with these criteria.

Methylated B3GAT2 and ZNF793 Are Potential Detection Biomarkers for Barrett's Esophagus.

Background: Barrett's esophagus (BE) is a preneoplastic condition in which normal esophageal squamous epithelium (SQ) is replaced by specialized intestinal metaplasia. It is the presumed precursor for esophageal adenocarcinoma (EAC) as well as the strongest risk factor for this cancer. Unfortunately, many patients with BE go undiagnosed under the current BE screening guidelines.

Use of a novel polyp "ruler snare" improves estimation of colon polyp size.

Background And Aims: Prior studies have demonstrated that endoscopists' estimates of polyp size are imprecise. The aim of this study was to determine whether a modified polypectomy "ruler snare" improves the accuracy of assessment of polyp size in real time without the use of additional devices.

Methods: Ten artificial polyps of predetermined sizes (4 to 25 mm) were affixed to the inside of a colon model.

Genetic and Epigenetic Alterations in Barrett's Esophagus and Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) develops from Barrett's esophagus (BE), wherein normal squamous epithelia is replaced by specialized intestinal metaplasia in response to chronic gastroesophageal acid reflux. BE can progress to low- and high-grade dysplasia, intramucosal, and invasive carcinoma. Both BE and EAC are characterized by loss of heterozygosity, aneuploidy, specific genetic mutations, and clonal diversity.

Differences in DNA methylation signatures reveal multiple pathways of progression from adenoma to colorectal cancer.

Background & Aims: Genetic and epigenetic alterations contribute to the pathogenesis of colorectal cancer (CRC). There is considerable molecular heterogeneity among colorectal tumors, which appears to arise as polyps progress to cancer. This heterogeneity results in different pathways to tumorigenesis.

Patterns of DNA methylation in the normal colon vary by anatomical location, gender, and age.

Alterations in DNA methylation have been proposed to create a field cancerization state in the colon, where molecular alterations that predispose cells to transformation occur in histologically normal tissue. However, our understanding of the role of DNA methylation in field cancerization is limited by an incomplete characterization of the methylation state of the normal colon. In order to determine the colon's normal methylation state, we extracted DNA from normal colon biopsies from the rectum, sigmoid, transverse, and ascending colon and assessed the methylation status of the DNA by pyrosequencing candidate loci as well as with HumanMethylation450 arrays.