Background Prophylactic total gastrectomy (PTG) is a risk-reducing strategy considered in individuals at high risk for diffuse gastric cancer (DGC) associated with germline CDH1 pathogenic variants. Methods A systematic literature search (PubMed, Scopus) was conducted to identify studies that performed PTGs in CDH1 carriers. Data were analysed using a random-effects generalised linear mixed model. Cochran's Q test was used to assess the heterogeneity between studies. Forest plots were used to display study-specific estimates, and the pooled estimates were calculated within three subsequent cohort periods (2001-2010; 2011-2020; 2021-2025). Statistical analyses were performed using R software. Results A total of 21 studies were considered out of 302 originally identified, including a total of 967 CDH1 carriers. PTG was performed in 62.9% of CDH1 pathogenic variant carriers. Advanced DGC (>pT1a) was detected in 1.1% and <= pT1a in 79% in postoperative PTG specimens. The majority of PTGs were reported from North America (58.9%). The pooled proportion of PTG decreased from 83.2% (95% CI 61.0% to 94.0%) in 2001-2010 to 71.0% (95% CI 59.0% to 80.7%) in 2011-2020 and to 67.5% (95% CI 48.9% to 81.8%) in 2021-2025 (p for trend=0.12). Conclusion About 60% of PTGs were reported from North America. The majority of the lesions were classified as pT1a. PTG indication has been progressively and constantly decreasing during the last years considered. This can be related to the recent genetic analyses reporting a lower DGC risk in CDH1 carriers and with the improvement in detection of early lesions during endoscopy. PROSPERO registration number CRD420261368873.
Background Mainstreaming, in which genetic testing is shifted outside clinical genetics, can improve access to genetic testing. This is being explored in several countries, including Canada, the USA and the UK. However, standardised practice within a jurisdiction helps ensure equitable high-quality access. This study aimed to evaluate consistency in the implementation of cancer genetics mainstreaming across Ontario, Canada.Methods Adult cancer genetics centres in Ontario were emailed an online survey in June 2025, which was completed by mainstreaming implementation leads. Results were anonymised and analysed in aggregate.Results Of 18 centres contacted, 13 responded; 12/13 reported having implemented cancer genetics mainstreaming. All mainstreaming centres offered pathways for breast, ovarian, prostate and pancreatic cancers, primarily based on personal history criteria. Most centres did not mainstream for other cancer sites but were planning to expand. A 19-gene hereditary breast/ovarian/prostate panel was most commonly ordered. There was variation in the timepoint of genetics service involvement. Turnaround times for expedited results were relatively consistent (median 21 days, IQR 18-22), whereas turnaround times for routine results varied widely (median 50 days, IQR 36-94).Conclusion Across Ontario, centres were generally consistent in mainstreaming the most common indications. Opportunities to improve quality and equity include reducing variability in routine turnaround time, standardising management pathways for negative results and streamlining ordering to align with eligibility criteria. Some centres cited limited genetics knowledge as an implementation barrier, though engagement improved over time. Ongoing evaluation of mainstreaming can support consistent access to care.
Satellite DNAs (satDNAs) are repetitive sequences that play important structural and functional roles in vertebrate genomes; however, their genomic composition and behavior during meiosis remain poorly understood in geckos. Here, we investigated the satellitome of the Central American banded gecko (Coleonyx mitratus) using bioinformatic and cytogenetic approaches. We identified fifteen candidate satDNA sequences representing at least fourteen satDNA families and mapped their distribution on mitotic and meiotic chromosomes. Most satellites were concentrated in constitutive heterochromatin regions. One of the satDNA families, CmitSat-10-58, showed compact signals associated with the core of the synaptonemal complex on most chromosomes and co-localized with anti-centromere antibodies, suggesting a possible role in centromeric function. A heterochromatin region on chromosome 6 containing two satDNA families showed delayed synapsis and excessive stretching during the pachytene stage. Differences in satDNA composition between the X and Y chromosomes may be associated with their delayed synapsis. Our results provide new insight into the organization, chromosomal distribution, and potential functional significance of satellite DNA in gecko genomes, and support further investigation of the relationship between repetitive DNA, heterochromatin organization, and chromosome dynamics during meiosis.
The protein kinase Mps1 (also known as TTK) is a critical regulator of the spindle assembly checkpoint (SAC) and genomic stability, and its frequent overexpression in human malignancies has established it as a compelling oncology target. Over the past two decades, drug discovery efforts have evolved from early tool compounds to selective inhibitors and clinical candidates. However, clinical translation has faced significant hurdles, notably dose-limiting toxicities and the emergence of drug resistance. This review provides a comprehensive and critical overview of Mps1-targeted therapy, integrating its fundamental mitotic and extra-mitotic functions, such as its crosstalk with the p53 and DNA damage response pathways, with its prognostic and predictive biomarker value. We systematically analyse the landscape of Mps1 inhibitors, covalent modifiers, and targeted protein degradation strategies like PROTACs. Furthermore, we examine the molecular mechanisms driving resistance, including kinase domain point mutations and downstream anaphase-promoting complex/cyclosome (APC/C) alterations, and highlight rational combination regimens with immunotherapy, DNA repair inhibitors, and taxanes as promising avenues to overcome current limitations and enhance therapeutic efficacy.
The r-X1 deletion can induce nondisjunction and terminal deficiencies in maize B and normal A chromosomes during megaspore division; however, to date, only one case of B chromosome deficiency (Bdef) with a breakpoint in the third distal heterochromatin of the B chromosome has been analyzed. In this study, we examined r-X1-containing progeny from maternal r-X1 plants carrying two B chromosomes, and an additional 18 potential Bdefs of varying lengths smaller than the B chromosome were observed, suggesting that the r-X1 deletion leads to random breakages of the B chromosome. Three of these Bdefs (designated Bdef-2, Bdef-3, and Bdef-5) with breakpoints in the proximal euchromatin, the second heterochromatin and the fourth heterochromatin of the B chromosome, respectively, were successfully propagated and further analyzed. Transmission analysis revealed that all three Bdefs lost the ability to undergo nondisjunction during the second pollen mitosis, whereas the presence of the B chromosome restored this ability. Furthermore, it is hypothesized that specific regions of the B chromosome existed to suppress the meiotic loss of univalent B chromosomes in both female and male plants. Finally, using these three Bdefs, eight B chromosome-specific polymerase chain reaction markers were physically mapped more precisely onto the B chromosome. Our results suggest that Bdefs induced by the r-X1 deletion can serve as a new resource for studying structure and function of the maize B chromosome.
