Optimising biomarkers for accurate ependymoma diagnosis, prognostication and stratification within International Clinical Trials: A BIOMECA study

BACKGROUND: Accurate identification of brain tumour molecular subgroups is increasingly important. We aimed to establish the most accurate and reproducible ependymoma subgroup biomarker detection techniques, across 147 cases from International Society of Pediatric Oncology (SIOP) Ependymoma II trial participants, enrolled in the pan-European "Biomarkers of Ependymoma in Children and Adolescents (BIOMECA)" study. METHODS: Across six European BIOMECA laboratories we evaluated epigenetic profiling (DNA methylation array); immunohistochemistry (IHC) for nuclear p65-RELA, H3K27me3, and Tenascin-C; copy number analysis via FISH and MLPA (1q, CDKN2A), and MIP and DNA methylation array (genome-wide copy number evaluation); analysis of ZFTA- and YAP1-fusions by RT-PCR and sequencing, Nanostring and break-apart FISH. RESULTS: DNA Methylation profiling classified 65.3% (n=96/147) of cases as EPN-PFA and 15% (n=22/147) as ST-ZFTA fusion-positive. Immunohistochemical loss of H3K27me3 was a reproducible and accurate surrogate marker for EPN-PFA (sensitivity 99-100% across three centres). IHC for p65-RELA, FISH, and RNA-based analyses effectively identified ZFTA- and YAP1- fused supratentorial ependymomas. Detection of 1q gain using FISH exhibited only 57% inter-centre concordance and low sensitivity and specificity whilst MIP, MLPA and DNA methylation-based approaches demonstrated greater accuracy. CONCLUSIONS: We confirm, in a prospective trial cohort, that H3K27me3 immunohistochemistry is a robust EPN-PFA biomarker. Tenascin-C should be abandoned as a PFA marker. DNA methylation and MIP arrays are effective tools for copy number analysis of 1q gain, 6q and CDKN2A loss whilst FISH is inadequate. Fusion detection was successful, but rare novel fusions need more extensive technologies. Finally, we propose test sets to guide future diagnostic approaches

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Dealing with difference: Contested place identities in two northern Scandinavian cities

In an era of culturally driven growth, urban identities are of central importance for the branding of cities. However, urban identities are under constant re-negotiation as cities’ populations become more diverse. In northern Scandinavia, some cities have developed on what were traditionally Indigenous lands but have failed to acknowledge the role these roots and histories have played in shaping the city’s identity. As the numbers of Indigenous people living in cities grow and they begin to assert their right to the city, the relationship between a city’s ‘majority population’ identity and its ‘Indigenous’ identity may become contested. Looking at the northern Scandinavian cities of Tromsø (Norway) and Umeå (Sweden), we study the conflicts that have arisen around the cities’ place identity. In Tromsø, the conflicts concerned joining the Sámi Administration Area. Whereas, in Umeå, the Sámi identity of the city was contested in relation to the inauguration of Umeå as European Capital of Culture 2014. Drawing on theories of place identity, social justice and the right to the city and analysing representations of place identity in the local media and public fora, we discuss the importance of change and reproduction of urban identities and power relations in the two cities. We conclude that contestation can open up space for change and challenge the city’s dominant power relations, encouraging a resurgent politics of recognition of Indigenous identities rather than a conciliatory form of settler-state recognition that (re)produces and maintains colonial relations