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Testicular germ cell tumours (TGCT), which comprise seminoma and non-seminoma subtypes, are the most common cancers in young men. In this study, we present a comprehensive whole genome sequencing analysis of adult TGCTs. Leveraging samples from participants recruited via the UK National Health Service and data from the Genomics England 100,000 Genomes Project, our results provide an extended description of genomic elements underlying TGCT pathogenesis. This catalogue offers a comprehensive, high-resolution map of copy number alterations, structural variation, and key global genome features, including mutational signatures and analysis of extrachromosomal DNA amplification. This study establishes correlations between genomic alterations and histological diversification, revealing divergent evolutionary trajectories among TGCT subtypes. By reconstructing the chronological order of driver events, we identify a subgroup of adult TGCTs undergoing relatively late whole genome duplication. Additionally, we present evidence that human leukocyte antigen loss is a more prevalent mechanism of immune disruption in seminomas. Collectively, our findings provide valuable insights into the developmental and immune modulatory processes implicated in TGCT pathogenesis and progression. Testicular germ cell tumours (TGCT) are the most common cancers in young men. Here, the authors analyse the genomic landscape of TGCT using data from the Genomics England 100,000 Genomes Project, revealing divergent evolutionary trajectories and the prevalence of human leukocyte antigen loss.

Background Up to 80% of cases of prostate cancer present with multifocal independent tumour lesions leading to the concept of a field effect present in the normal prostate predisposing to cancer development. In the present study we applied Whole Genome DNA Sequencing (WGS) to a group of morphologically normal tissue ( n  = 51), including benign prostatic hyperplasia (BPH) and non-BPH samples, from men with and men without prostate cancer. We assess whether the observed genetic changes in morphologically normal tissue are linked to the development of cancer in the prostate. Results Single nucleotide variants ( P  = 7.0 × 10 –03 , Wilcoxon rank sum test) and small insertions and deletions (indels, P  = 8.7 × 10 –06 ) were significantly higher in morphologically normal samples, including BPH, from men with prostate cancer compared to those without. The presence of subclonal expansions under selective pressure, supported by a high level of mutations, were significantly associated with samples from men with prostate cancer ( P  = 0.035, Fisher exact test). The clonal cell fraction of normal clones was always higher than the proportion of the prostate estimated as epithelial ( P  = 5.94 × 10 –05 , paired Wilcoxon signed rank test) which, along with analysis of primary fibroblasts prepared from BPH specimens, suggests a stromal origin. Constructed phylogenies revealed lineages associated with benign tissue that were completely distinct from adjacent tumour clones, but a common lineage between BPH and non-BPH morphologically normal tissues was often observed. Compared to tumours, normal samples have significantly less single nucleotide variants ( P  = 3.72 × 10 –09 , paired Wilcoxon signed rank test), have very few rearrangements and a complete lack of copy number alterations. Conclusions Cells within regions of morphologically normal tissue (both BPH and non-BPH) can expand under selective pressure by mechanisms that are distinct from those occurring in adjacent cancer, but that are allied to the presence of cancer. Expansions, which are probably stromal in origin, are characterised by lack of recurrent driver mutations, by almost complete absence of structural variants/copy number alterations, and mutational processes similar to malignant tissue. Our findings have implications for treatment (focal therapy) and early detection approaches.

Cancer progression involves the sequential accumulation of genetic alterations that cumulatively shape the tumour phenotype. In prostate cancer, tumours can follow divergent evolutionary trajectories that lead to distinct subtypes, but the causes of this divergence remain unclear. While causal inference could elucidate the factors involved, conventional methods are unsuitable due to the possibility of unobserved confounders and ambiguity in the direction of causality. Here, we propose a method that circumvents these issues and apply it to genomic data from 829 prostate cancer patients. We identify several genetic alterations that drive divergence as well as others that prevent this transition, locking tumours into one trajectory. Further analysis reveals that these genetic alterations may cause each other, implying a positive-feedback loop that accelerates divergence. Our findings provide insights into how cancer subtypes emerge and offer a foundation for genomic surveillance strategies aimed at monitoring the progression of prostate cancer.

Cancer progression involves the sequential accumulation of genetic alterations that cumulatively shape the tumour phenotype. In prostate cancer, tumours can follow divergent evolutionary trajectories that lead to distinct subtypes, but the causes of this divergence remain unclear. While causal inference could elucidate the factors involved, conventional methods are unsuitable due to the possibility of unobserved confounders and ambiguity in the direction of causality. Here, we propose a method that circumvents these issues and apply it to genomic data from 829 prostate cancer patients. We identify several genetic alterations that drive divergence as well as others that prevent this transition, locking tumours into one trajectory. Further analysis reveals that these genetic alterations may cause each other, implying a positive-feedback loop that accelerates divergence. Our findings provide insights into how cancer subtypes emerge and offer a foundation for genomic surveillance strategies aimed at monitoring the progression of prostate cancer.

Copy number variations (CNVs) are large genetic variations detected among the individuals of every multicellular organism examined so far. These variations are believed to play an important role in the evolution and adaptation of species. In plants, little is known about the characteristics of CNVs, particularly regarding the rates at which they are generated and the mechanics of their transmission from a generation to the next. Here, we used SNP-array raw intensity data for 55 two-generations families (3663 individuals) to scan the gene space of the conifer tree Picea glauca (Moench) Voss for CNVs. We were particularly interested in the abundance, inheritance, spontaneous mutation rate spectrum and the evolutionary consequences they may have on the standing genetic variation of white spruce. Our findings show that CNVs affect a small proportion of the gene space and are predominantly copy number losses. CNVs were either inherited or generated through de novo events. De novo CNVs present high rates of spontaneous mutations that vary for different genes and alleles and are correlated with gene expression levels. Most of the inherited CNVs (70%) are transmitted from the parents in violation of Mendelian expectations. These transmission distortions can cause considerable frequency changes between generations and be dependent on whether the heterozygote parents contribute as male or female. Transmission distortions were also influenced by the partner genotype and the parents genetic background. This study provides new insights into the effects of different evolutionary forces on copy number variations based on the analysis of a perennial plant.

This comparative study investigates the effectiveness of two teaching methods, individual verbal encouragement and collective verbal encouragement, in enhancing the technical–tactical skills and mood state of obese students during handball matches. This study employs a randomized controlled design and involves 28 overweight students (50% females), age: 17.4 ± 2.08 years and BMI: 26.8 ± 1.5 for females and 27.3 ± 2.1 for males. Technical–tactical skills are assessed through performance metrics (individual evaluation proposal by Gréhaigne) such as Ball Played (BP), Conquered Ball (CB), Lost Ball (LB), Shoots/Goals, Conservation index, and defensive index, while mood states are evaluated using pre- and post-tests (BRUMS Scale). Results reveal that individual verbal encouragement significantly enhances technical–tactical skills and positively influences the mood state of overweight students compared to collective verbal encouragement. Boys in Session 1 with VEI displayed a significantly higher number of ball plays (mean difference = 0.94 standard deviations, p = 0.004) and conquered balls (mean difference = 0.78 standard deviations, p = 0.006) compared to VEC. They also had a lower number of Lost Balls (mean difference = −0.62 standard deviations, p = 0.018) and a higher shooting efficiency (Shoots/Goals ratio, mean difference = 0.67 standard deviations; p = 0.013). Similar trends were observed in Session 2, with VEI, again, demonstrating advantages. Girls exhibited analogous improvements with VEI in both sessions. Notably, these performance enhancements coincided with positive emotional changes, with VEI leading to a greater decrease in depression and fatigue scores for both boys and girls. The study highlights the importance of tailoring teaching methods to the specific needs of overweight students in the context of handball, emphasizing the effectiveness of individualized verbal encouragement for skill development and emotional well-being. These findings offer practical implications for educators and coaches involved in physical education, advocating for personalized approaches to optimize learning experiences for overweight students in sports settings.

This study compares the effects of coach verbal encouragement (CVE) and peer verbal encouragement (PVE) on CrossFit-specific one-repetition maximum (1-RM) strength, functional endurance, and psychophysiological assessments. A total of 36 sports science students (18 males, 18 females; mean age: 21.3 ± 0.5 years) participated in a randomized, counterbalanced crossover study in which 1-RM strength and endurance assessment sessions were undertaken under PVE, CVE, and no verbal encouragement (NVE) on separate days. Here, 1-RM strength was assessed through squat, deadlift, and bench press exercises, while endurance was evaluated using 8 min time trials (8MTT). Following the physical assessments, psychophysiological evaluations were conducted using the Borg Rating of Perceived Exertion (RPE) and the Feeling Scale (FS). The findings revealed that, after PVE, all the 1-RM strength test, 8MTT, RPE, and FS values exhibited significant increases compared to those of CVE (p [<0.001–<0.01], r = −0.84 [large]) and NVE (p [<0.001–<0.05], r [−0.43–0.52] [small]). Exceptions were noted in 1-RM-deadlift (p > 0.05, r = −0.43 [small]) and 1-RM-bench-press (p > 0.05, r = −0.43 [small]), where CVE demonstrated higher scores (1-RM-squat, 8MTT, RPE, and FS) (p [<0.001–<0.05], r = −0.64 [large]) in comparison to NVE. In conclusion, the study established that PVE is more impactful than CVE in enhancing CrossFit-specific 1-RM strength, functional endurance, and psychophysiological assessment performance. These findings suggest that coaches/teachers should consider involving their athletes in the reinforcement process for evaluated peers. This collaborative approach may not only optimize performance outcomes but also foster a supportive and motivational training environment.