Methylation Markers in Prostate Biopsies Are Prognosticators for Late Biochemical Recurrence and Therapy after Surgery in Prostate Cancer Patients.

After diagnosis of prostate cancer is confirmed by a positive biopsy, the tumor may be surgically removed via radical prostatectomy (RP). However, many prostate cancer patients experience biochemical recurrence after surgery and/or undergo salvage radiotherapy or hormone therapy. Timely treatment is required to prevent the spread of disease in these cases, and biopsy tissue may hold potential for disease prognostication before surgery is ever performed.

An integrative DNA methylation model for improved prognostication of postsurgery recurrence and therapy in prostate cancer patients.

Purpose: Patients with clinically localized, high-risk prostate cancer are often treated with surgery, but exhibit variable prognosis requiring long-term monitoring. An ongoing challenge for such patients is developing optimal strategies and biomarkers capable of differentiating between men at risk of early recurrence (<3 years) that will benefit from adjuvant therapies and men at risk of late recurrence (>5 years) who will benefit from long-term monitoring and/or salvage therapies.

Patients And Methods: DNA methylation changes for 12 genes associated with disease progression were analyzed in 453 prostate tumors.

GBX2 Methylation Is a Novel Prognostic Biomarker and Improves Prediction of Biochemical Recurrence Among Patients with Prostate Cancer Negative for Intraductal Carcinoma and Cribriform Architecture.

Background: Tumor intraductal carcinoma/cribriform architecture (IDC/C) is associated with an unfavorable prognosis and biochemical recurrence (BCR) in prostate cancer (PCa). Up to 70% of PCa patients are IDC/C-negative, but it is estimated that 20% of these cases still experience BCR. Thus, biomarkers for better detection of aggressive disease in IDC/C-negative patients are required.

Distinct DNA methylation alterations are associated with cribriform architecture and intraductal carcinoma in Gleason pattern 4 prostate tumors.

The aim of the present study was to explore DNA methylation aberrations in association with cribriform architecture and intraductal carcinoma (IDC) of the prostate, as there is robust evidence that these morphological features are associated with aggressive disease and have significant clinical implications. Herein, the associations of a panel of seven known prognostic DNA methylation biomarkers with cribriform and IDC features were examined in a series of 91 Gleason pattern (GP) 4 tumors derived from Gleason score 7 radical prostatectomies. Gene specific DNA methylation was compared between cribriform and/or IDC positive vs.

Modulation of transcription factor binding and epigenetic regulation of the MLH1 CpG island and shore by polymorphism rs1800734 in colorectal cancer.

The MLH1 promoter polymorphism rs1800734 is associated with MLH1 CpG island hypermethylation and expression loss in colorectal cancer (CRC). Conversely, variant rs1800734 is associated with MLH1 shore, but not island, hypomethylation in peripheral blood mononuclear cell DNA. To explore these distinct patterns, MLH1 CpG island and shore methylation was assessed in CRC cell lines stratified by rs1800734 genotype.

The dynamic DNA methylation landscape of the shore is altered by -93G>A polymorphism in normal tissues and colorectal cancer.

Background: Colorectal cancers (CRCs) undergo distinct genetic and epigenetic alterations. Expression of (), a mismatch repair gene that corrects DNA replication errors, is lost in up to 15% of sporadic tumours due to mutation or, more commonly, due to DNA methylation of its promoter CpG island. A single nucleotide polymorphism (SNP) in the CpG island of (-93G>A or rs1800734) is associated with CpG island hypermethylation and decreased expression in CRC tumours.

Epigenome-Wide DNA Methylation Profiling Identifies Differential Methylation Biomarkers in High-Grade Bladder Cancer.

Epigenetic changes, including CpG island hypermethylation, occur frequently in bladder cancer (BC) and may be exploited for BC detection and distinction between high-grade (HG) and low-grade (LG) disease. Genome-wide methylation analysis was performed using Agilent Human CpG Island Microarrays to determine epigenetic differences between LG and HG cases. Pathway enrichment analysis and functional annotation determined that the most frequently methylated pathways in HG BC were enriched for anterior/posterior pattern specification, embryonic skeletal system development, neuron fate commitment, DNA binding, and transcription factor activity.

Promoter methylation of ITF2, but not APC, is associated with microsatellite instability in two populations of colorectal cancer patients.

Background: Aberrant Wnt signaling activation occurs commonly in colorectal carcinogenesis, leading to upregulation of many target genes. APC (adenomatous polyposis coli) is an important component of the β-catenin destruction complex, which regulates Wnt signaling, and is often mutated in colorectal cancer (CRC). In addition to mutational events, epigenetic changes arise frequently in CRC, specifically, promoter hypermethylation which silences tumor suppressor genes.

Beyond the island: epigenetic biomarkers of colorectal and prostate cancer.

Epigenetic dysregulation is a common feature across all cancer types. Epigenetic mechanisms, from DNA methylation to histone modifications, allow for a vast number of cellular phenotypes to be created from the same genetic material. Just as certain genetic changes play a key role in tumor initiation and progression, epigenetic changes may also set the course of tumor development and be required for malignant transformation.

MLH1 region polymorphisms show a significant association with CpG island shore methylation in a large cohort of healthy individuals.

Single nucleotide polymorphisms (SNPs) are the most common form of genetic variation. We previously demonstrated that SNPs (rs1800734, rs749072, and rs13098279) in the MLH1 gene region are associated with MLH1 promoter island methylation, loss of MLH1 protein expression, and microsatellite instability (MSI) in colorectal cancer (CRC) patients. Recent studies have identified less CpG-dense "shore" regions flanking many CpG islands.