9 results on '"Mathias Stiller"'
Search Results
2. TP53 co-mutations in advanced lung adenocarcinoma: comparative bioinformatic analyses suggest ambivalent character on overall survival alongside KRAS, STK11 and KEAP1 mutations
- Author
-
Armin Frille, Myriam Boeschen, Hubert Wirtz, Mathias Stiller, Hendrik Bläker, and Maximilian von Laffert
- Subjects
NSCLC ,lung adenocarcinoma ,KRAS ,STK11 ,KEAP1 ,TP53 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundRecently, we could show that the co-mutations of KRAS + KEAP1, STK11 + KEAP1 and KRAS + STK11 + KEAP1 lead to a significantly shorter median overall survival (mOS) in patients with lung cancer across treatments by analyzing multiple dataset. TP53, a tumor suppressor gene, plays a crucial role in regulating cell cycle progression. Its mutations occur in approximately 40-50% of non-small lung cancer (NSCLC). Co-occurrence of all four mentioned mutations has been a matter of debate for years. The aim of this study was to assess the distribution of these four mutations and the influence of the different co-mutational patterns on survival.MethodsWe present a comparative bioinformatic analysis and refer to data of 4,109 patients with lung adenocarcinoma (LUAD).ResultsMost of the mutations within the LUAD belong to TP53-only (29.0%), quadruple-negative (25.9%) and KRAS-only (13.4%). Whereas TP53-mutations seem to have protective effects in the context of further KEAP1- and KRAS + KEAP1-alterations (improved mOS), their role seems contrary if acquired in an already existing combination of mutations as KRAS + STK11, KRAS + STK11 + KEAP1 and STK11 + KEAP1. TP53 co-mutations had a negative influence on KRAS-only mutated LUAD (mOS reduced significantly by more than 30%).DiscussionThese data underline the need for complex mutational testing to estimate prognosis more accurately in patients with advanced LUAD.
- Published
- 2024
- Full Text
- View/download PDF
3. TERT expression is associated with metastasis from thin primaries, exhausted CD4+ T cells in melanoma and with DNA repair across cancer entities.
- Author
-
Christina Katharina Kuhn, Jaroslawna Meister, Sophia Kreft, Mathias Stiller, Sven-Holger Puppel, Anne Zaremba, Björn Scheffler, Vivien Ullrich, Torsten Schöneberg, Dirk Schadendorf, and Susanne Horn
- Subjects
Medicine ,Science - Abstract
Telomerase reverse transcriptase (TERT) promoter mutations occur frequently in cancer, have been associated with increased TERT expression and cell proliferation, and could potentially influence therapeutic regimens for melanoma. As the role of TERT expression in malignant melanoma and the non-canonical functions of TERT remain understudied, we aimed to extend the current knowledge on the impact of TERT promoter mutations and expression alterations in tumor progression by analyzing several highly annotated melanoma cohorts. Using multivariate models, we found no consistent association for TERT promoter mutations or TERT expression with the survival rate in melanoma cohorts under immune checkpoint inhibition. However, the presence of CD4+ T cells increased with TERT expression and correlated with the expression of exhaustion markers. While the frequency of promoter mutations did not change with Breslow thickness, TERT expression was increased in metastases arising from thinner primaries. As single-cell RNA-sequencing (RNA-seq) showed that TERT expression was associated with genes involved in cell migration and dynamics of the extracellular matrix, this suggests a role of TERT during invasion and metastasis. Co-regulated genes found in several bulk tumors and single-cell RNA-seq cohorts also indicated non-canonical functions of TERT related to mitochondrial DNA stability and nuclear DNA repair. This pattern was also evident in glioblastoma and across other entities. Hence, our study adds to the role of TERT expression in cancer metastasis and potentially also immune resistance.
- Published
- 2023
- Full Text
- View/download PDF
4. A new genus of horse from Pleistocene North America
- Author
-
Peter D Heintzman, Grant D Zazula, Ross DE MacPhee, Eric Scott, James A Cahill, Brianna K McHorse, Joshua D Kapp, Mathias Stiller, Matthew J Wooller, Ludovic Orlando, John Southon, Duane G Froese, and Beth Shapiro
- Subjects
stilt-legged equids ,Haringtonhippus francisci ,systematics ,ancient DNA ,radiocarbon dating ,morphometrics ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
The extinct ‘New World stilt-legged’, or NWSL, equids constitute a perplexing group of Pleistocene horses endemic to North America. Their slender distal limb bones resemble those of Asiatic asses, such as the Persian onager. Previous palaeogenetic studies, however, have suggested a closer relationship to caballine horses than to Asiatic asses. Here, we report complete mitochondrial and partial nuclear genomes from NWSL equids from across their geographic range. Although multiple NWSL equid species have been named, our palaeogenomic and morphometric analyses support the idea that there was only a single species of middle to late Pleistocene NWSL equid, and demonstrate that it falls outside of crown group Equus. We therefore propose a new genus, Haringtonhippus, for the sole species H. francisci. Our combined genomic and phenomic approach to resolving the systematics of extinct megafauna will allow for an improved understanding of the full extent of the terminal Pleistocene extinction event.
- Published
- 2017
- Full Text
- View/download PDF
5. Palaeogenomes of Eurasian straight-tusked elephants challenge the current view of elephant evolution
- Author
-
Matthias Meyer, Eleftheria Palkopoulou, Sina Baleka, Mathias Stiller, Kirsty E H Penkman, Kurt W Alt, Yasuko Ishida, Dietrich Mania, Swapan Mallick, Tom Meijer, Harald Meller, Sarah Nagel, Birgit Nickel, Sven Ostritz, Nadin Rohland, Karol Schauer, Tim Schüler, Alfred L Roca, David Reich, Beth Shapiro, and Michael Hofreiter
- Subjects
Palaeoloxodon antiquus ,Elephas antiquus ,ancient DNA ,paleogenomes ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
The straight-tusked elephants Palaeoloxodon spp. were widespread across Eurasia during the Pleistocene. Phylogenetic reconstructions using morphological traits have grouped them with Asian elephants (Elephas maximus), and many paleontologists place Palaeoloxodon within Elephas. Here, we report the recovery of full mitochondrial genomes from four and partial nuclear genomes from two P. antiquus fossils. These fossils were collected at two sites in Germany, Neumark-Nord and Weimar-Ehringsdorf, and likely date to interglacial periods ~120 and ~244 thousand years ago, respectively. Unexpectedly, nuclear and mitochondrial DNA analyses suggest that P. antiquus was a close relative of extant African forest elephants (Loxodonta cyclotis). Species previously referred to Palaeoloxodon are thus most parsimoniously explained as having diverged from the lineage of Loxodonta, indicating that Loxodonta has not been constrained to Africa. Our results demonstrate that the current picture of elephant evolution is in need of substantial revision.
- Published
- 2017
- Full Text
- View/download PDF
6. Mitochondrial phylogenomics of modern and ancient equids.
- Author
-
Julia T Vilstrup, Andaine Seguin-Orlando, Mathias Stiller, Aurelien Ginolhac, Maanasa Raghavan, Sandra C A Nielsen, Jacobo Weinstock, Duane Froese, Sergei K Vasiliev, Nikolai D Ovodov, Joel Clary, Kristofer M Helgen, Robert C Fleischer, Alan Cooper, Beth Shapiro, and Ludovic Orlando
- Subjects
Medicine ,Science - Abstract
The genus Equus is richly represented in the fossil record, yet our understanding of taxonomic relationships within this genus remains limited. To estimate the phylogenetic relationships among modern horses, zebras, asses and donkeys, we generated the first data set including complete mitochondrial sequences from all seven extant lineages within the genus Equus. Bayesian and Maximum Likelihood phylogenetic inference confirms that zebras are monophyletic within the genus, and the Plains and Grevy's zebras form a well-supported monophyletic group. Using ancient DNA techniques, we further characterize the complete mitochondrial genomes of three extinct equid lineages (the New World stilt-legged horses, NWSLH; the subgenus Sussemionus; and the Quagga, Equus quagga quagga). Comparisons with extant taxa confirm the NWSLH as being part of the caballines, and the Quagga and Plains zebras as being conspecific. However, the evolutionary relationships among the non-caballine lineages, including the now-extinct subgenus Sussemionus, remain unresolved, most likely due to extremely rapid radiation within this group. The closest living outgroups (rhinos and tapirs) were found to be too phylogenetically distant to calibrate reliable molecular clocks. Additional mitochondrial genome sequence data, including radiocarbon dated ancient equids, will be required before revisiting the exact timing of the lineage radiation leading up to modern equids, which for now were found to have possibly shared a common ancestor as far as up to 4 Million years ago (Mya).
- Published
- 2013
- Full Text
- View/download PDF
7. Genomic evidence for island population conversion resolves conflicting theories of polar bear evolution.
- Author
-
James A Cahill, Richard E Green, Tara L Fulton, Mathias Stiller, Flora Jay, Nikita Ovsyanikov, Rauf Salamzade, John St John, Ian Stirling, Montgomery Slatkin, and Beth Shapiro
- Subjects
Genetics ,QH426-470 - Abstract
Despite extensive genetic analysis, the evolutionary relationship between polar bears (Ursus maritimus) and brown bears (U. arctos) remains unclear. The two most recent comprehensive reports indicate a recent divergence with little subsequent admixture or a much more ancient divergence followed by extensive admixture. At the center of this controversy are the Alaskan ABC Islands brown bears that show evidence of shared ancestry with polar bears. We present an analysis of genome-wide sequence data for seven polar bears, one ABC Islands brown bear, one mainland Alaskan brown bear, and a black bear (U. americanus), plus recently published datasets from other bears. Surprisingly, we find clear evidence for gene flow from polar bears into ABC Islands brown bears but no evidence of gene flow from brown bears into polar bears. Importantly, while polar bears contributed
- Published
- 2013
- Full Text
- View/download PDF
8. Influence of climate warming on arctic mammals? New insights from ancient DNA studies of the collared lemming Dicrostonyx torquatus.
- Author
-
Stefan Prost, Nickolay Smirnov, Vadim B Fedorov, Robert S Sommer, Mathias Stiller, Doris Nagel, Michael Knapp, and Michael Hofreiter
- Subjects
Medicine ,Science - Abstract
BackgroundGlobal temperature increased by approximately half a degree (Celsius) within the last 150 years. Even this moderate warming had major impacts on Earth's ecological and biological systems, especially in the Arctic where the magnitude of abiotic changes even exceeds those in temperate and tropical biomes. Therefore, understanding the biological consequences of climate change on high latitudes is of critical importance for future conservation of the species living in this habitat. The past 25,000 years can be used as a model for such changes, as they were marked by prominent climatic changes that influenced geographical distribution, demographic history and pattern of genetic variation of many extant species. We sequenced ancient and modern DNA of the collared lemming (Dicrostonyx torquatus), which is a key species of the arctic biota, from a single site (Pymva Shor, Northern Pre Urals, Russia) to see if climate warming events after the Last Glacial Maximum had detectable effects on the genetic variation of this arctic rodent species, which is strongly associated with a cold and dry climate.ResultsUsing three dimensional network reconstructions we found a dramatic decline in genetic diversity following the LGM. Model-based approaches such as Approximate Bayesian Computation and Markov Chain Monte Carlo based Bayesian inference show that there is evidence for a population decline in the collared lemming following the LGM, with the population size dropping to a minimum during the Greenland Interstadial 1 (Bølling/Allerød) warming phase at 14.5 kyrs BP.ConclusionOur results show that previous climate warming events had a strong influence on genetic diversity and population size of collared lemmings. Due to its already severely compromised genetic diversity a similar population reduction as a result of the predicted future climate change could completely abolish the remaining genetic diversity in this population. Local population extinctions of collared lemmings would have severe effects on the arctic ecosystem, as collared lemmings are a key species in the trophic interactions and ecosystem processes in the Arctic.
- Published
- 2010
- Full Text
- View/download PDF
9. Correction: Influence of Climate Warming on Arctic Mammals? New Insights from Ancient DNA Studies of the Collared Lemming.
- Author
-
Stefan Prost, Nickolay Smirnov, Vadim B. Fedorov, Robert S. Sommer, Mathias Stiller, Doris Nagel, Michael Knapp, and Michael Hofreiter
- Subjects
Medicine ,Science - Published
- 2010
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.