Biology subjects

McCabe, A.

Publications and source records attributed to McCabe, A..

2 recordsLinked to original sources

bioRxiv2026

Tube to Tumour: an integrative epigenomic analysis of DNA methylation in high-grade serous ovarian cancer and precursor serous tubal intraepithelial carcinoma

Serous tubal intraepithelial carcinoma (STIC) is a known precursor of high-grade serous ovarian cancer (HGSOC). Yet, molecular events driving progression from STIC to HGSOC remain poorly defined. Aberrant DNA methylation is a hallmark of cancer, yet its role in early HGSOC remains unclear. We performed a comprehensive meta-analysis of publicly available Illumina Infinium DNA methylation EPIC array datasets assessing 255 samples comprising STIC, HGSOC, and histologically normal fallopian tube tissues. We mapped DNA methylation alterations during early tumorigenesis, identified conserved methylation patterns across STIC and HGSOC, and assessed RNA-sequencing data to define transcriptional consequences within genomic and epigenomic landscapes. STIC and HGSOC exhibited widespread DNA hypomethylation relative to normal tissue, accompanied by focal hypermethylation in CpG islands and 5' regulatory regions. DNA Hypomethylation intensifies during progression from STIC to HGSOC, particularly in cis-regulatory enhancer domains and intergenic regions. We identified 11,660 CpG sites and 447 genomic regions with conserved DNA methylation patterns across STIC and HGSOC. Within these, 70 genes showed coordinated DNA methylation and expression changes, including TRIM15, NKAPL, and RIPPLY3. These findings reveal that epigenetic remodelling occurs in STIC lesions, prior to malignant transformation. DNA methylation alterations at regulatory regions may drive invasion and offer novel avenues for early detection and targeted intervention.

Cancer Biology↗

bioRxiv2023

Arabidopsis cell suspension culture and RNA sequencing reveal regulatory networks underlying plant programmed cell death.

Programmed cell death (PCD) facilitates targeted elimination of redundant, damaged, or infected cells via genetically controlled pathways. In plants, PCD is often an essential component of normal development and can also mediate responses to abiotic and biotic stress stimuli. However, studying the transcriptional regulation of this fundamental process is hindered by difficulties in sampling small groups of cells undergoing PCD that are often buried within the bulk of living plant tissue. We addressed this challenge by using RNA sequencing (RNA-Seq) of Arabidopsis thaliana suspension cells, a system that allows precise monitoring of PCD activation and progression. The use of three PCD-inducing treatments (salicylic acid, heat and critical dilution), in combination with three cell death modulators (3- methyladenine, lanthanum chloride and conditioned medium), allowed isolation of candidate core and stimuli-specific PCD genes, inference of underlying gene regulatory networks and identification of putative transcriptional regulators. This analysis underscored cell cycle disturbance and the repression of both pro-survival stress responses and mitochondrial retrograde signalling as key elements of the PCD-associated transcriptional signature in plants. Further, phenotyping of twenty Arabidopsis T-DNA insertion mutants in selected candidate genes confirmed a role for several in PCD and stress tolerance regulation, and validated the potential of these generated resources to identify novel genes involved in plant PCD pathways and/or stress tolerance in plants.

plant biology↗