Cancer epigenetics and epitranscriptomics

Chromatin and transcriptome studies in myelomonocytic leukemia stem cells revealed repression of retroelements and immune genes. Restoring these pathways by co-inhibiting DNA methylation and H3K9me2 enables selective targeting of leukemic cells.

The role of histone deacetylases (HDACs) in glioblastoma brain tumour stem cells (BTSCs) remains to be explored. Here, pharmacological inhibition and genetic loss of function approaches show that HDAC2 leads to the maintenance of BTSC growth and self-renewal through its association with the components of the TGF-β signalling pathway.

Leukemias with ambiguous lineage require further characterisation. Here, the authors perform epigenomic and transcriptomic analysis of a subgroup of such leukemias with CpG Island Methylator Phenotype and propose that epigenetic dysregulation and not genetic lesions explains their mixed phenotype.

The relevance of post-translational modifications in pancreatic cancer remains insufficiently explored. Here, the authors report that ZDHHC20-mediated S-Palmitoylation of the m6A reader YTHDF3 stabilizes MYC mRNA to promote the progression of KRAS-mutant pancreatic cancer.

Cuproptosis regulation in tumors is unclear. Here the authors find that copper promotes METTL16 lactylation, inducing cuproptosis via stabilizing FDX1 in gastric cancer. Targeting lactyl-METTL16 and cuproptosis offers a potential feasible strategy for cancer therapy.

Class IIA isoform specific inhibition represents an attractive therapeutic target in KMT2A-rearranged infant acute lymphoblastic leukemia.

DNA methylation from cell-free DNA (cfDNA) can be profiled using whole genome bisulfite sequencing (WGBS). Here, the authors develop a computational method, FinaleMe, that predicts DNA methylation and tissues of-origin in cfDNA and validate its performance using paired deep and shallow-coverage whole-genome sequencing (WGS) and WGBS data.

Cell free RNA is a potentially valuable resource to detect cancer, however, its low concentration in plasma can limit usefulness. Here, the authors devise a library preparation method from 100ul of plasma, and apply to multiple cancer types to detect and classify cancer patients

Sahm et al. evaluate clinical, imaging, and molecular data from a small cohort of patients with concurrent multiple sclerosis (MS) and gliomas. They report differential methylation of some immune-related loci in tumors from patients with MS, and that inflammatory disease activity can increase in these patients after brain tumor radiotherapy.

Radiation dosimetry are critical for the medical management of individuals exposed to ionizing radiation (IR). Here, authors show that the RNA m6A levels of Ncoa4, Ate1 and Fgf22 genes in peripheral blood cells could serve as dosimetry of IR exposure.