http://demo1.journalmanager.net/ Journal Manager Demo for Scholarly Journals en daily 1 Mon, 01 Jun 2026 00:00:00 +0330 Mon, 01 Jun 2026 00:00:00 +0330 http://demo1.journalmanager.net/article_1.html Aberrant DNA methylation is an early hallmark of malignant transformation. We profiled the genome-wide methylation landscape of 480 pre-malignant and tumour specimens across six tissue types, identifying 1,284 differentially methylated regions that separate pre-malignant from invasive disease. Hypermethylation of developmental transcription-factor loci emerged as the earliest detectable event, preceding copy-number change in 71% of cases. These findings position methylation profiling as a candidate substrate for early-detection assays. http://demo1.journalmanager.net/article_2.html A subpopulation of drug-tolerant persister cells underlies relapse after targeted therapy. We characterised persister states in lung adenocarcinoma using paired single-cell transcriptomic and chromatin-accessibility profiling across eight patient-derived models. Persisters converged on a shared quiescent programme marked by lysosomal expansion and dependence on GPX4. Pharmacological ferroptosis induction depleted the persister reservoir and delayed resistance in vivo. http://demo1.journalmanager.net/article_3.html Intratumoural heterogeneity shapes treatment response. We applied single-cell DNA and RNA sequencing to 36 colorectal tumours spanning disease stages, reconstructing clonal phylogenies at single-cell resolution. Branched evolution dominated in mismatch-repair-proficient tumours, while deficient tumours showed punctuated bursts of mutation. Subclonal diversity at diagnosis predicted shorter progression-free survival independently of stage. http://demo1.journalmanager.net/article_4.html Circulating tumour DNA enables non-invasive cancer detection. We developed a next-generation sequencing assay targeting methylation and mutation signals simultaneously, validated in a prospective cohort of 1,150 participants. The combined assay achieved 84% sensitivity at 99.4% specificity for stage I-II disease, substantially exceeding mutation-only detection. Tissue-of-origin prediction was correct in 88% of positive cases. http://demo1.journalmanager.net/article_5.html The tumour suppressor p53 safeguards genome integrity. We modelled p53 loss in organoids and tracked the emergence of structural variation over 40 passages. p53 deficiency produced a rapid accumulation of chromothriptic events concentrated on chromosomes 8 and 17, accompanied by whole-genome doubling in a third of lines. Restoration of p53 function arrested but did not reverse the acquired instability. http://demo1.journalmanager.net/article_6.html The tumour microenvironment is epigenetically remodelled during progression. We mapped methylation changes in stromal and immune compartments of breast tumours using sorted-population bisulfite sequencing. Cancer-associated fibroblasts acquired a distinct hypomethylated enhancer landscape driving chemokine secretion, while infiltrating T cells showed progressive methylation at effector loci consistent with exhaustion. http://demo1.journalmanager.net/article_7.html Synthetic lethality exploits tumour-specific dependencies. We performed genome-wide CRISPR screens in BRCA-mutant cancer lines to map DNA-repair vulnerabilities beyond PARP. Loss of POLQ and USP1 emerged as the strongest selective dependencies, and combined inhibition overcame acquired PARP-inhibitor resistance in patient-derived xenografts. http://demo1.journalmanager.net/article_8.html Mismatch-repair deficiency predicts immunotherapy benefit, but finer stratification is needed. We analysed DNA-repair signatures across 2,400 treated patients, deriving a composite repair-deficiency score. The score stratified response within microsatellite-instability-high tumours and identified a responsive subgroup among proficient tumours that current criteria would exclude. http://demo1.journalmanager.net/article_9.html Evasion of apoptosis is a core hallmark of cancer and a driver of therapy resistance. We dissected apoptotic priming in matched pre- and post-treatment biopsies using BH3 profiling. Resistant tumours showed reduced mitochondrial priming and a shift in dependence from BCL-2 to MCL-1, which BH3-mimetic combination therapy reversed in ex vivo culture. http://demo1.journalmanager.net/article_10.html Polygenic background modifies penetrance in hereditary cancer. We built a polygenic risk model in 18,000 carriers of high-penetrance variants across five syndromes. Polygenic score shifted lifetime risk by up to 31 percentage points within the same monogenic genotype, with the largest effect in Lynch syndrome. Incorporating polygenic background materially changes surveillance recommendations. http://demo1.journalmanager.net/article_11.html Telomere attrition precipitates a state of chromosomal instability that fuels tumour heterogeneity. We characterised telomere dynamics across 312 aggressive carcinomas using long-read sequencing. Tumours with critically short telomeres showed a fivefold excess of fusion-bridge-breakage events, and telomerase reactivation timing separated two distinct evolutionary trajectories. http://demo1.journalmanager.net/article_12.html KRAS-mutant cancers remain difficult to treat. We performed genome-wide CRISPR knockout screens across 28 KRAS-mutant tumour models to map synthetic-lethal interactions. Dependencies clustered by tissue of origin rather than KRAS allele, and SHOC2 loss was selectively lethal across pancreatic models irrespective of downstream pathway configuration.