| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Arevalo-Martinez, D. L., et al.
(author)
-
Ideas and perspectives: Land-ocean connectivity through groundwater
- 2023
-
In: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 20:3, s. 647-662
-
Journal article (peer-reviewed)abstract
- For millennia, humans have gravitated towards coastlines for theirresource potential and as geopolitical centres for global trade. A basicrequirement ensuring water security for coastal communities relies on adelicate balance between the supply and demand of potable water. Theinteraction between freshwater and saltwater in coastal settings is,therefore, complicated by both natural and human-driven environmentalchanges at the land-sea interface. In particular, ongoing sea-level rise,warming and deoxygenation might exacerbate such perturbations. In thiscontext, an improved understanding of the nature and variability ofgroundwater fluxes across the land-sea continuum is timely yet remains outof reach. The flow of terrestrial groundwater across the coastal transitionzone and the extent of freshened groundwater below the present-dayseafloor are receiving increased attention in marine and coastal sciencesbecause they likely represent a significant yet highly uncertain componentof (bio)geochemical budgets and because of the emerging interest in thepotential use of offshore freshened groundwater as a resource. At the sametime, "reverse" groundwater flux from offshore to onshore is of prevalentsocio-economic interest, as terrestrial groundwater resources arecontinuously pressured by over-pumping and seawater intrusion in many coastalregions worldwide. An accurate assessment of the land-ocean connectivitythrough groundwater and its potential responses to future anthropogenicactivities and climate change will require a multidisciplinary approachcombining the expertise of geophysicists, hydrogeologists, (bio)geochemistsand modellers. Such joint activities will lay the scientific basis forbetter understanding the role of groundwater in societally relevant issuessuch as climate change, pollution and the environmental status of thecoastal oceans within the framework of the United Nations SustainableDevelopment Goals. Here, we present our perspectives on future researchdirections to better understand land-ocean connectivity through groundwater,including the spatial distributions of the essential hydrogeologicalparameters, highlighting technical and scientific developments and brieflydiscussing the societal relevance of that connectivity in rapidly changing coastal oceans.
|
|
| 6. |
|
|
| 7. |
- Northcott, Paul A, et al.
(author)
-
Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.
- 2014
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 511:7510, s. 428-428
-
Journal article (peer-reviewed)abstract
- Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.
|
|
| 8. |
- Voronina, N, et al.
(author)
-
The age of adult pilocytic astrocytoma cells
- 2021
-
In: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 40:16, s. 2830-2841
-
Journal article (peer-reviewed)abstract
- Adult pilocytic astrocytomas (PAs) have been regarded as indistinguishable from pediatric PAs in terms of genome-wide expression and methylation patterns. It has been unclear whether adult PAs arise early in life and remain asymptomatic until adulthood, or whether they develop during adulthood. We sought to determine the age and origin of adult human PAs using two types of “marks” in the genomic DNA. First, we analyzed the DNA methylation patterns of adult and pediatric PAs to distinguish between PAs of different anatomic locations (n = 257 PA and control brain tissues). Second, we measured the concentration of nuclear bomb test-derived 14C in genomic DNA (n = 14 cases), which indicates the time point of the formation of human cell populations. Our data suggest that adult and pediatric PAs developing in the infratentorial brain are closely related and potentially develop from precursor cells early in life, whereas supratentorial PAs might show age and location-specific differences.
|
|
| 9. |
- Elsir, T., et al.
(author)
-
PROX1 is a predictor of survival for gliomas WHO grade II
- 2011
-
In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 104:11, s. 1747-1754
-
Journal article (peer-reviewed)abstract
- Background:The clinical course of World Health Organisation grade II gliomas remains variable and their time point of transformation into a more malignant phenotype is unpredictable. Identification of biological markers that can predict prognosis in individual patients is of great clinical value. PROX1 is a transcription factor that has a critical role in the development of various organs. PROX1 has been ascribed both oncogenic and tumour suppressive functions in human cancers. We have recently shown that PROX1 may act as a diagnostic marker for high-grade gliomas. The aim of this study was to address the prognostic value of PROX1 in grade II gliomas.Methods:A total of 116 samples were evaluated for the presence of PROX1 protein. The number of immunopositive cells was used as a variable in survival analysis, together with established prognostic factors for this patient group.Results:Higher PROX1 protein was associated with poor outcome. In the multivariate analysis, PROX1 was identified as an independent factor for survival (P=0.024), together with the presence of mutated isocitrate dehydrogenase 1 R132H protein, and with combined losses of chromosomal arms 1p/19q in oligodendrocytic tumours.Conclusion:PROX1 is a novel predictor of survival for grade II gliomas.
|
|
| 10. |
- Keck, Michaela Kristina, et al.
(author)
-
Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification
- 2023
-
In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 145:1, s. 49-69
-
Journal article (peer-reviewed)abstract
- Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0–14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.
|
|
