Devil facial tumour 1 (DFT1) is a transmissible cancer clone endangering the Tasmanian devil. The expansion of DFT1 across Tasmania has been documented, but little is known of its evolutionary history. We analysed genomes of 648 DFT1 tumours collected throughout the disease range between 2003 and 2018. DFT1 diverged early into five clades, three spreading widely and two failing to persist. One clade has replaced others at several sites, and rates of DFT1 coinfection are high. DFT1 gradually accumulates copy number variants (CNVs), and its telomere lengths are short but constant. Recurrent CNVs reveal genes under positive selection, sites of genome instability, and repeated loss of a small derived chromosome. Cultured DFT1 cell lines have increased CNV frequency and undergo highly reproducible convergent evolution. Overall, DFT1 is a remarkably stable lineage whose genome illustrates how cancer cells adapt to diverse environments and persist in a parasitic niche.

Many patients with glioma, primary brain tumors, suffer from poorly understood executive functioning deficits before and/or after tumor resection. We aimed to test whether frontoparietal network centrality of multilayer networks, allowing for integration across multiple frequencies, relates to and predicts executive functioning in glioma. Patients with glioma (n = 37) underwent resting-state magnetoencephalography and neuropsychological tests assessing word fluency, inhibition, and set shifting before (T1) and one year after tumor resection (T2). We constructed binary multilayer networks comprising six layers, with each layer representing frequency-specific functional connectivity between source-localized time series of 78 cortical regions. Average frontoparietal network multilayer eigenvector centrality, a measure for network integration, was calculated at both time points. Regression analyses were used to investigate associations with executive functioning. At T1, lower multilayer integration (p = 0.017) and epilepsy (p = 0.006) associated with poorer set shifting (adj. R2 = 0.269). Decreasing multilayer integration (p = 0.022) and not undergoing chemotherapy at T2 (p = 0.004) related to deteriorating set shifting over time (adj. R2 = 0.283). No significant associations were found for word fluency or inhibition, nor did T1 multilayer integration predict changes in executive functioning. As expected, our results establish multilayer integration of the frontoparietal network as a cross-sectional and longitudinal correlate of executive functioning in glioma patients. However, multilayer integration did not predict postoperative changes in executive functioning, which together with the fact that this correlate is also found in health and other diseases, limits its specific clinical relevance in glioma.

Background Glioma is associated with pathologically high neuronal activity around the tumor, which associates with faster tumor progression in patients. Concurrently, patients with glioma have local and widespread disturbances of the functional brain network as measured with magnetoencephalography (MEG) such as higher network clustering (the extent to which regions connected to a particular area are also connected to each other) and locally altered integrative connectivity (for instance assessed with a centrality measure). How local neuronal activity and nodal network properties relate to each other has yet to be investigated. Material and Methods We obtained eyes-closed resting-state MEG in 95 glioma patients before tumor resection and 57 matched healthy controls (HC). Broadband power (BBP, 0.5-48Hz) was used as a proxy for neuronal activity. The local clustering coefficient (CC) and eigenvector centrality (EC) were calculated for the functional network in the lower frequency bands (delta, theta, alpha). We compared averaged nodal network properties and local BBP between peritumoral (regions partially overlapping with the tumor) and contralateral homologue regions in patients and compared these to averaged values in HC. Linear mixed models were used to relate nodal CC and EC to local BBP. Results were corrected for multiple comparisons and deemed significant at alpha 0.05. Results The peritumoral area was significantly more active than the non-peritumoral homologue in patients, and showed pathologically higher activity in comparison to HCs. Pathologically high neuronal activity was restricted to the peritumoral areas and not found in the contralateral homologue. However, patients’ functional network was disturbed throughout the brain in terms of pathologically high clustering, but not with regards to centrality. Whereas high activity related to high centrality in HCs and patients alike, high activity seemed to relate to low clustering in homologue regions in patients but not HCs, potentially indicating that lower neuronal activity relates to pathologically high clustering in these patients. Conclusion Glioma patients show pathologically high brain activity around the tumor and whole-brain disturbances in local network clustering, while integrative connectivity is preserved. We also find that the relationship between neuronal activity and functional network properties is complex in these patients, further underlining the importance of investigating how local activity may impact global network topology in order to understand how neuron-glioma interactions shape brain functioning.