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128 results for “cancer evolution”
Deciphering genomic evolution of metastatic organotropism with 535 paired primary lung cancers and metastases
<p>Scripts and processed data used in the analyses of the manuscript:</p> <p><em>Deciphering genomic evolution of metastatic organotropism with 535 paired primary lung cancers and metastases.</em></p>
Supplementary data: The molecular evolution of cancer associated genes in mammals
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Function and evolution of B-Raf loop dynamics relevant to cancer recurrence under drug inhibition
<p>Oncogenic mutations in the kinase domain of the B-Raf protein have long been associated with cancers involving the RAF-MEK-ERK pathway. One constitutive ERK activating mutation in B-Raf, the V600E (valine to glutamate) replacement occurring adjacent to a site of threonine phosphorylation (T599) occurs in many types of cancer, and in a large percentage of certain cancers, such as melanoma. Because natural ATP binding activity and the V600E mutation are both known to alter the physical behavior of the activation loop in the ATP binding domain, this system is especially amenable to comparative functional analyses using molecular dynamics of drug classes and genetic variants at all-atom resolution. Here, we employ machine learning enabled identification of functionally conserved protein dynamics to compare how disease pertinent molecular variations impact conserved loop dynamics during the binding of four ATP competitive B-Raf inhibitors (sorafenib, vemurafenib, dabrafenib, and PLX7904) that differ in their effectiveness in preventing cancer recurrence. We demonstrate that drug development targeting B-Raf has progressively moved towards ATP competitive inhibitors that demonstrate less tendency to mimic the functional dynamic shifts associated with ATP binding in this domain. We argue this functional dynamic mimicry in first generation B-Raf inhibitors increases the side effect of hyperactivation (i.e. inducing MAPK activation in non-tumorous cells in the absence of secondary mutation). Within the context of the binding interaction of each inhibitor, we compare the functional dynamic impacts of V600E and other sensitizing and drug resistance causing mutations in the activation and P-loops, confirming sites of low mutational tolerance in these two functional regions. Lastly, we investigate V600E sensitivity of B-Raf loop dynamics in an evolutionary context, demonstrating that while it probably shares partial origin with its early evolution in primitive eukaryotes, the functional sensitivity to V600E was secondarily increased during early jawed vertebrate evolution.</p>
Dataset to article "Distinct traits of structural and regulatory evolutional conser-vation of human genes with specific focus on major cancer mo-lecular pathways"
<p>Abstract: Evolution of protein coding genes has both structural and regulatory components. The first can be assessed by measuring the ratio of non-synonymous to synonymous nucleotide sub-stitutions. The second component can be measured as the normalized proportion of transposable elements that used as the regulatory elements. For the first time, we characterized in parallel the regulatory and structural evolutionary profiles for 10,890 human genes and 2,972 molecular pathways. We observed ~0.1 correlation between the structural and regulatory metrics at the gene level, which appeared much higher (~0.4) at the pathway level. We deposited the data in the publicly available database RetroSpect accessible at https://retrospect.oncobox.com. We also analyzed evolutionary dynamics of six cancer pathways of two major axes: Notch/WNT/Hedgehog and AKT/mTOR/EGFR. The Hedgehog pathway had both components slower, whereas the Akt pathway had clearly accelerated structural evolution. In particular, the major hub nodes Akt and beta-catenin showed both components strongly decreased, whereas two major regulators of Akt TCL1 and CTMP had outstandingly high evolutionary rates. We al-so noticed structural conservation of serine/threonine kinases and the genes related to guanosine metabolism in cancer signaling: GPCRs, G proteins, and small regulatory GTPases (Src, Rac, Ras); however, this was compensated by the accelerated regulatory evolution.</p>
An Analysis of Treatment Timelines for Lung Cancer Patients Across System Evolutions
ClinicalTrials.gov study NCT03535766. IPD Sharing: NO. Countries: 1. Publications: 3.
Evolution of the Therapeutic Care in Metastatic Breast Cancer From 2008
ClinicalTrials.gov study NCT03275311. IPD Sharing: NO. Countries: 1. Publications: 52.
Retrospective Observational Study About Evolution of Patients With Breast Cancer in Hospitals From GEICAM Group
ClinicalTrials.gov study NCT03210974. IPD Sharing: NO. Countries: 1. Publications: 1.
Evolution of the Physical Condition in Treated Cancer Patients
ClinicalTrials.gov study NCT03956641. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Evolution of the Therapeutic Care in Lung Cancer in France Since 2015 (ESME LC)
ClinicalTrials.gov study NCT03848052. IPD Sharing: Not stated. Countries: 1. Publications: 12.
A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer
ClinicalTrials.gov study NCT03425292. IPD Sharing: YES. Countries: 1. Publications: 1.
On-treatment Surveillance of Tumor Evolution and Response to Systemic Treatment in Bile Duct and Liver Cancer
ClinicalTrials.gov study NCT06877637. IPD Sharing: NO. Countries: 1. Publications: 1.
Evolution of the Heart Function When Monitoring Immunotherapies Anti-cancerous Inhibiting PD-1
ClinicalTrials.gov study NCT03313544. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Evolution of the Therapeutic Care in Ovarian Cancer From 2011
ClinicalTrials.gov study NCT03275298. IPD Sharing: NO. Countries: 1. Publications: 5.
Breast Cancer Evolution During Neoadjuvant Systemic Therapy
ClinicalTrials.gov study NCT06681064. IPD Sharing: Not stated. Countries: 1. Publications: 1.
TRAcking Non-small Cell Lung Cancer Evolution Through Therapy (Rx)
ClinicalTrials.gov study NCT01888601. IPD Sharing: Not stated. Countries: 1. Publications: 10.
Data from: Anthropogenic selection enhances cancer evolution in Tasmanian devil tumours
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Evolution and lineage dynamics of a transmissible cancer in Tasmanian devils
<p>Devil facial tumour 1 (DFT1) is a transmissible cancer clone endangering the Tasmanian devil. The expansion of DFT1 across Tasmania has been documented, but little is known of its evolutionary history. We analysed genomes of 648 DFT1 tumours collected throughout the disease range between 2003 and 2018. DFT1 diverged early into five clades, three spreading widely and two failing to persist. One clade has replaced others at several sites, and rates of DFT1 co-infection are high. DFT1 gradually accumulates copy number variants (CNVs) and its telomere lengths are short but constant. Recurrent CNVs reveal genes under positive selection, sites of genome instability and repeated loss of a small derived chromosome. Cultured DFT1 cell lines have increased CNV frequency and undergo highly reproducible convergent evolution. Overall, DFT1 is a remarkably stable lineage whose genome illustrates how cancer cells adapt to diverse environments and persist in a parasitic niche.</p>
Data from: Evolution of increased survival in RNA viruses specialized on cancer-derived cells
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Data from: Sweepstake evolution revealed by population-genetic analysis of copy-number alterations in single genomes of breast cancer
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TRPS1 drives heterochromatic origin refiring and cancer genome evolution [copy number]
GEO Series GSE135598. Homo sapiens. 12 samples. Type: Genome variation profiling by SNP array; SNP genotyping by SNP array.
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Understand access before you commit
These curated guides explain access requirements, typical timelines, costs, and reuse considerations for widely used research datasets.
Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.