| 1. |
- Ameline, Baptiste, et al.
(författare)
-
Methylation and copy number profiling : emerging tools to differentiate osteoblastoma from malignant mimics?
- 2022
-
Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952. ; 35:9, s. 1204-1211
-
Tidskriftsartikel (refereegranskat)abstract
- Rearrangements of the transcription factors FOS and FOSB have recently been identified as the genetic driver event underlying osteoid osteoma and osteoblastoma. Nuclear overexpression of FOS and FOSB have since then emerged as a reliable surrogate marker despite limitations in specificity and sensitivity. Indeed, osteosarcoma can infrequently show nuclear FOS expression and a small fraction of osteoblastomas seem to arise independent of FOS/FOSB rearrangements. Acid decalcification and tissue preservation are additional factors that can negatively influence immunohistochemical testing and make diagnostic decision-making challenging in individual cases. Particularly aggressive appearing osteoblastomas, also referred to as epithelioid osteoblastomas, and osteoblastoma-like osteosarcoma can be difficult to distinguish, underlining the need for additional markers to support the diagnosis. Methylation and copy number profiling, a technique well established for the classification of brain tumors, might fill this gap. Here, we set out to comprehensively characterize a series of 77 osteoblastomas by immunohistochemistry, fluorescence in-situ hybridization as well as copy number and methylation profiling and compared our findings to histologic mimics. Our results show that osteoblastomas are uniformly characterized by flat copy number profiles that can add certainty in reaching the correct diagnosis. The methylation cluster formed by osteoblastomas, however, so far lacks specificity and can be misleading in individual cases.
|
|
| 2. |
- Bratic, Ivana, et al.
(författare)
-
Mitochondrial DNA level, but not active replicase, is essential for Caenorhabditis elegans development
- 2009
-
Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 37:6, s. 1817-1828
-
Tidskriftsartikel (refereegranskat)abstract
- A number of studies showed that the development and the lifespan of Caenorhabditis elegans is dependent on mitochondrial function. In this study, we addressed the role of mitochondrial DNA levels and mtDNA maintenance in development of C. elegans by analyzing deletion mutants for mitochondrial polymerase gamma (polg-1(ok1548)). Surprisingly, even though previous studies in other model organisms showed necessity of polymerase gamma for embryonic development, homozygous polg-1(ok1548) mutants had normal development and reached adulthood without any morphological defects. However, polg-1 deficient animals have a seriously compromised gonadal function as a result of severe mitochondrial depletion, leading to sterility and shortened lifespan. Our results indicate that the gonad is the primary site of mtDNA replication, whilst the mtDNA of adult somatic tissues mainly stems from the developing embryo. Furthermore, we show that the mtDNA copy number shows great plasticity as it can be almost tripled as a response to the environmental stimuli. Finally, we show that the mtDNA copy number is an essential limiting factor for the worm development and therefore, a number of mechanisms set to maintain mtDNA levels exist, ensuring a normal development of C. elegans even in the absence of the mitochondrial replicase.
|
|
| 3. |
- Hench, Jürgen, et al.
(författare)
-
Spatio-temporal reference model of Caenorhabditis elegans embryogenesis with cell contact maps
- 2009
-
Ingår i: Developmental Biology. - : Elsevier BV. - 0012-1606 .- 1095-564X. ; 333:1, s. 1-13
-
Tidskriftsartikel (refereegranskat)abstract
- The nematode Caenorhabditis elegans has been used as a model for developmental biology for decades. Still, the few publicly available spatio-temporal (4D) data sets have conflicting information regarding variability of cell positions and are not well-suited for a standard 4D embryonic model, due to compression. We have recorded six uncompressed embryos, and determined their lineage and 4D coordinates, including nuclear radii, until the end of gastrulation. We find a remarkable degree of stability in the cell positions, as well as little rotational movement, which allowed us to combine the data into a single reference model of C. elegans embryogenesis. Using Voronoi decomposition we generated the list of all predicted cell contacts during early embryogenesis and calculated these contacts up to the similar to 150 cell stage, and find that about 1500 contacts last 2.5 min or longer. The cell contact map allows for comparison of multiple 4D data sets, e. g., mutants or related species, at the cellular level. A comparison of our uncompressed 4D model with a compressed embryo shows that up to 40% of the cell contacts can be different. To visualize the 4D model interactively we developed a software utility. Our model provides an anatomical resource and can serve as foundation to display 4D expression data, a basis for developmental systems biology.
|
|
| 4. |
- Hench, Jürgen, et al.
(författare)
-
The Homeobox Genes of Caenorhabditis elegans and Insights into Their Spatio-Temporal Expression Dynamics during Embryogenesis
- 2015
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
-
Tidskriftsartikel (refereegranskat)abstract
- Homeobox genes play crucial roles for the development of multicellular eukaryotes. We have generated a revised list of all homeobox genes for Caenorhabditis elegans and provide a nomenclature for the previously unnamed ones. We show that, out of 103 homeobox genes, 70 are co-orthologous to human homeobox genes. 14 are highly divergent, lacking an obvious ortholog even in other Caenorhabditis species. One of these homeobox genes encodes 12 homeodomains, while three other highly divergent homeobox genes encode a novel type of double homeodomain, termed HOCHOB. To understand how transcription factors regulate cell fate during development, precise spatio-temporal expression data need to be obtained. Using a new imaging framework that we developed, Endrov, we have generated spatio-temporal expression profiles during embryogenesis of over 60 homeobox genes, as well as a number of other developmental control genes using GFP reporters. We used dynamic feedback during recording to automatically adjust the camera exposure time in order to increase the dynamic range beyond the limitations of the camera. We have applied the new framework to examine homeobox gene expression patterns and provide an analysis of these patterns. The methods we developed to analyze and quantify expression data are not only suitable for C. elegans, but can be applied to other model systems or even to tissue culture systems.
|
|
| 5. |
|
|
