bims-dinmec 2025-08-31 papers

Issue of 2025–08–31
three papers selected by
Lorena Ancona, Humanitas Research

Epigenetics Chromatin. 2025 Aug 25. 18(1): 57

Comparison of current methods for genome-wide DNA methylation profiling.

Ana Regina de Abreu, Joe Ibrahim, Vasileios Lemonidis, Ligia Mateiu, Guy Van Camp, Ken Op de Beeck.

BACKGROUND: DNA methylation is an epigenetic mechanism involved in gene regulation and cellular differentiation. Accurate and comprehensive assessment of DNA methylation patterns is thus essential for understanding their role in various biological processes and disease mechanisms. Bisulfite sequencing has long been the default method for analyzing methylation marks due to its single-base resolution, but the associated DNA degradation poses a concern. Although several methods have been proposed to circumvent this issue, there is no clear consensus on which method might be better suited for specific study designs.
RESULTS: We conducted a comparative evaluation of four DNA methylation detection approaches: whole-genome bisulfite sequencing (WGBS), Illumina methylation microarray (EPIC), enzymatic methyl-sequencing (EM-seq) and third-generation sequencing by Oxford Nanopore Technologies (ONT). DNA methylation profiles were assessed across three human genome samples derived from tissue, cell line, and whole blood. We systematically compared these methods in terms of resolution, genomic coverage, methylation calling accuracy, cost, time, and practical implementation. EM-seq showed the highest concordance with WGBS, indicating strong reliability due to their similar sequencing chemistry. ONT sequencing, while showing lower agreement with WGBS and EM-seq, captured certain loci uniquely and enabled methylation detection in challenging genomic regions. Despite a substantial overlap in CpG detection among methods, each method identified unique CpG sites, emphasizing their complementary nature.
CONCLUSIONS: Our findings underscore the strengths and limitations of current DNA methylation detection methods. EM-seq and ONT emerge as robust alternatives to WGBS and EPIC, offering unique advantages: EM-seq delivers consistent and uniform coverage, while ONT excels in long-range methylation profiling and access to challenging genomic regions. These insights provide practical guidance for method selection based on specific experimental goals.

Keywords: Coverage; Cytosine; DNA methylation; Enzymatic methyl-sequencing (EM-seq); Epigenomics; Illumina EPIC array; Oxford Nanopore Technologies (ONT); Whole-genome bisulfite sequencing (WGBS)

DOI: https://doi.org/10.1186/s13072-025-00616-3

World J Gastrointest Oncol. 2025 Aug 15. 17(8): 107412

Role of circulating tumor DNA methylation in gastric cancer initiation and progression: A comprehensive review.

Hai-Yu Huang, Jiang Lan, Wei Zhuang.

Circulating tumor DNA (ctDNA) is the free DNA released by tumor or circulating tumor cells, which is associated with many tumor characteristics and can be used as a biomarker for early screening, monitoring, prognosis, and prediction of therapeutic response in patients with cancer. The field of gastric cancer is very attractive because there are no high-quality screening, monitoring, or prediction methods. Gastric cancer is characterized by great tumor heterogeneity, great differences in genetic and epigenetic characteristics among different subgroups of gastric cancer, and high sensitivity and specificity of methylated ctDNA, which is conducive to the identification of tumor genotypes and the formulation of accurate diagnostic and treatment strategies. In addition, many studies have confirmed that methylated DNA has unique advantages in predicting treatment response, adjuvant therapy, and drug resistance and can be used to increase the efficacy of chemotherapy regimens, improve the chemotherapy response of patients in the future, and even treat multidrug resistance. However, methylated ctDNA also faces many problems, such as low sensitivity and specificity in a single target, limited association between some gastric cancer subtypes and ctDNA, risk of off-target effects, and lack of large-sample and high-quality clinical research evidence. This review mainly summarizes the current research on the DNA methylation of circulating gastric cancer tumors and links these findings with the early screening of gastric cancer, recurrence monitoring, and potential treatment opportunities. With the advancement of technology and the deepening of cross-research between doctors and professionals, ctDNA detection will reveal more disease information and become an important basis for the field of gastric cancer and precision medicine treatment.

Keywords: Biomarkers; Circulating tumor DNA; DNA methylation; Early screening; Gastric neoplasms

DOI: https://doi.org/10.4251/wjgo.v17.i8.107412

Genes (Basel). 2025 Jul 27. pii: 883. [Epub ahead of print]16(8):

Does BRCA Mutation Status Influence Ovarian Cancer Onset Timing and Patients' Treatment Outcomes?

Kaja Michalczyk, Agata Mokrzycka, Marianna Rudzińska, Barbara Michalczyk, Janusz Menkiszak, Anita Chudecka-Głaz.

BACKGROUND/OBJECTIVES: Mutations in the BRCA1 and BRCA2 genes are well-known risk factors for ovarian cancer. They are also associated with response to platinum-based chemotherapy; however, their definitive impact on patient prognosis remains not fully understood. This study aimed to investigate the influence of BRCA mutation status on the age of ovarian cancer onset and on treatment outcomes in patients with high-grade serous ovarian cancer.
METHODS: This single-center retrospective analysis included newly diagnosed FIGO stage III and IV HGSOC patients treated between June 2018 and April 2023. Patients' age, tumor histology, CA125 levels, BRCA mutation status, type of treatment (neoadjuvant or adjuvant chemotherapy), and surgical outcomes were collected and analyzed. Survival analyses were performed using the Kaplan-Meier method and log-rank test.
RESULTS: Pathogenic mutations were identified in 25 patients (15 in BRCA1, 10 in BRCA2). Patients with a BRCA mutation were diagnosed at a significantly younger age (median 58.78 years) compared to non-carriers (66.81 years; p < 0.001), with BRCA1 carriers being diagnosed the youngest (median 46.52 years). The study found no statistically significant difference in progression-free survival (PFS) between BRCA carriers and non-carriers. However, a significant improvement in overall survival (OS) was observed for patients with a BRCA1 mutation (p = 0.036). No significant OS difference was found for BRCA2 carriers.
CONCLUSIONS: BRCA mutations, particularly in the BRCA1 gene, are associated with an earlier onset ovarian cancer. BRCA1 mutation appears to be a favorable prognostic factor for overall survival in patients with HGSOC. Our findings demonstrate the clinical implications of different BRCA mutations and support the need for further research in larger cohorts to confirm their influence on prognostic effects.

Keywords: BRCA1; BRCA2; HGSOC; ovarian cancer

DOI: https://doi.org/10.3390/genes16080883