Anaplastic astrocytoma WHO grade III (A3) is a lethal brain tumor that often occurs in middle aged patients. Clinically, it is challenging to distinguish A3 from glioblastoma multiforme (GBM) WHO grade IV. To reveal the genetic landscape of this tumor type, we sequenced the exome of a cohort of A3s (n=16). For comparison and to illuminate the genomic landscape of other glioma subtypes, we also included in our study diffuse astrocytoma WHO grade II (A2, n=7), oligoastrocytoma WHO grade II (OA2, n=2), anaplastic oligoastrocytoma WHO grade III (OA3, n=4), and GBM (n=28). Exome sequencing of A3s identified frequent mutations in IDH1 (75%, 12/16), ATRX (63%, 10/16), and TP53 (82%, 13/16). In contrast, the majority of GBMs (75%, 21/28) did not contain IDH1 or ATRX mutations, and displayed a distinct spectrum of mutations. Finally, our study also identified novel genes that were not previously linked to this tumor type. In particular, we found mutations in Notch pathway genes (NOTCH1, NOTCH2, NOTCH4, NOTCH2NL), including a recurrent NOTCH1-A465Tmutation, in 31% (5/16) of A3s. This study suggests genetic signatures will be useful for the classification of gliomas.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039223 | PMC |
| http://dx.doi.org/10.18632/oncotarget.1505 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity.
Cell Rep
January 2025
Josep Carreras Leukaemia Research Institute (IJC), Badalona, Spain; Barcelona Supercomputing Center (BSC), Barcelona, Spain. Electronic address:
Tumors are complex ecosystems of interacting cell types. The concept of cancer hallmarks distills this complexity into underlying principles that govern tumor growth. Here, we explore the spatial distribution of cancer hallmarks across 63 primary untreated tumors from 10 cancer types using spatial transcriptomics.
View Article and Find Full Text PDFCharacterizing the omics landscape based on 10,000+ datasets.
Sci Rep
January 2025
Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
The characteristics of data produced by omics technologies are pivotal, as they critically influence the feasibility and effectiveness of computational methods applied in downstream analyses, such as data harmonization and differential abundance analyses. Furthermore, variability in these data characteristics across datasets plays a crucial role, leading to diverging outcomes in benchmarking studies, which are essential for guiding the selection of appropriate analysis methods in all omics fields. Additionally, downstream analysis tools are often developed and applied within specific omics communities due to the presumed differences in data characteristics attributed to each omics technology.
View Article and Find Full Text PDFExploring force-driven stochastic folding dynamics in mechano-responsive proteins and implications in phenotypic variation.
Nat Commun
January 2025
Department of Chemical Sciences, Indian Institute of Science Education and Research Mohali, Punjab, India.
Single-point mutations are pivotal in molecular zoology, shaping functions and influencing genetic diversity and evolution. Here we study three such genetic variants of a mechano-responsive protein, cadherin-23, that uphold the structural integrity of the protein, but showcase distinct genotypes and phenotypes. The variants exhibit subtle differences in transient intra-domain interactions, which in turn affect the anti-correlated motions among the constituent β-strands.
View Article and Find Full Text PDFLeveraging Epigenetic Alterations in Pancreatic Ductal Adenocarcinoma for Clinical Applications.
Semin Cancer Biol
January 2025
Biomedical Research Center, Slovak Academy of Sciences, Dubravska Cesta 9, 84505 Bratislava, Slovakia. Electronic address:
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by late detection and poor prognosis. Recent research highlights the pivotal role of epigenetic alter- ations in driving PDAC development and progression. These changes, in conjunction with genetic mutations, contribute to the intricate molecular landscape of the disease.
View Article and Find Full Text PDFLigand interaction landscape of transcription factors and essential enzymes in E. coli.
Cell
January 2025
Program in Bioinformatics, Boston University, Boston, MA 02215, USA; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Center for Network Systems Biology, Boston University, Boston, MA 02218, USA; Department of Chemistry, Boston University, Boston, MA 02215, USA; Department of Chemical Physiology and Biochemistry, Division of Oncological Sciences, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA. Electronic address:
Knowledge of protein-metabolite interactions can enhance mechanistic understanding and chemical probing of biochemical processes, but the discovery of endogenous ligands remains challenging. Here, we combined rapid affinity purification with precision mass spectrometry and high-resolution molecular docking to precisely map the physical associations of 296 chemically diverse small-molecule metabolite ligands with 69 distinct essential enzymes and 45 transcription factors in the gram-negative bacterium Escherichia coli. We then conducted systematic metabolic pathway integration, pan-microbial evolutionary projections, and independent in-depth biophysical characterization experiments to define the functional significance of ligand interfaces.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!