DNA methylation markers for early detection of women’s cancer: promise and challenges

Abstract

Breast, ovarian and endometrial cancers cause significant morbidity and mortality. Despite the presence of existing screening, diagnostic and treatment modalities, they continue to pose considerable unsolved challenges. Overdiagnosis is a growing problem in breast cancer screening and neither screening nor early diagnosis of ovarian or endometrial cancer is currently possible. Moreover, treatment of the diversity of these cancers presenting in the clinic is not sufficiently personalized at present. Recent technological advances, including reduced representation bisulfite sequencing, methylation arrays, digital PCR, next-generation sequencing and advanced statistical data analysis, enable the analysis of methylation patterns in cell-free tumor DNA in serum/plasma. Ongoing work is bringing these methods together for the analysis of samples from large clinical trials, which have been collected well in advance of cancer diagnosis. These efforts pave the way for the development of a noninvasive method that would enable us to overcome existing challenges to personalized medicine.

Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and circulating tumor DNA

“…Many studies have reported methylation changes in ovarian cancer [77] and a recent review summarizes the differences in the observed methylation patterns in the main histological subtypes of the disease, including HGSC [78]. DNA methylation changes have the potential to serve as biomarkers for early diagnosis of gynecological malignancies [79]. This is also observed in Table 2; only one study by Gifford et al [60] aimed to show the prognostic value of ctDNA methylation in ovarian cancer.…”

A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker

“…DNA hypermethylation in the regulatory regions of specific genes has been described as a potential early cancer marker with strategies for diagnostic or cancer screening procedures being developed (27 ). Most methods developed for DNA methylation analysis have used conventional quantitative PCR (qPCR) strategies with a few reports describing the use of droplet-based digital approaches for this purpose (21,28,29 ).…”

The potential of circulating nucleic acids as components of companion diagnostics for predicting and monitoring chemotherapy response

“…This method has high sensitivity and specificity and is suitable for quantification with a high dynamic range. For example, allele-specific ligation PCR, droplet digital PCR, PCR-restriction fragment length or methylation-specific PCR are applied for the measurement of DNA concentrations, and genetic and epigenetic alterations, respectively [49][50][51]. Specific amplifications of mature miRNAs can be permitted by the stem-loop primer method using stemloop-shaped primers [52], the polyA tailed PCR using polyadenylation enzymes and the TaqMan quantitative real-time PCR low-density array using format microfluidic cards in which preloaded PCR primers can simultaneously profile hundreds of miRNAs [53].…”

“…However, microarray is much less expensive than deep sequencing. The recent development of massively parallel sequencing (NGS, RNA-seq) technology has enabled profiling of DNA and RNA [51,55,56]. Although only a limited number of studies have analyzed circulating nucleic acids by deep sequencing, these reports have provided valuable information on circulating DNA and miRNA isoforms in serum and plasma [55,57].…”