8215 results for "canc*"

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• Bladder cancer subtyping study across 4 atezo clinical trials

  Checkpoint inhibitors targeting the PD-1/PD-L1 interaction have revolutionized cancer therapy across many indications. In urothelial carcinoma (UC), several PD-1/PD-L1 inhibitors have been approved for treatment in localized and metastatic disease. While these agents provide durable clinical benefit in a number of patients, the majority do not respond. A better understanding of the molecular mechanisms underlying response and resistance is needed to tailor existing treatments and develop new therapeutics in UC. We profiled tumors from 2803 patients from four late-stage randomized clinical trials evaluating the PD-L1 inhibitor atezolizumab in metastatic UC and muscle-invasive bladder cancer by RNA-seq, a targeted DNA panel, immunohistochemistry, and digital pathology. A machine learning algorithm identified four UC transcriptional subtypes, representing luminal desert, stromal, immune, and basal tumors. Overall survival benefit from atezolizumab over standard-of-care was observed in immune and basal tumors (45% of patients). Digital pathology showed enrichment of human interpretable features in specific molecular subtypes, and a self-supervised approach could classify molecular subtypes from H&E slides with high accuracy, suggesting that machine-based image interpretation could accelerate tumor molecular profiling. Somatic alterations showed limited capacity to identify responders. Finally, mechanisms of benefit with PD-L1 blockade appeared different in immune and basal tumors, with immune tumors benefiting from B/plasma cell enrichment, while basal tumors benefited from granulocyte enrichment. This study represents the largest integration of UC molecular and curated clinical data in randomized clinical trials to date, paving the way for prospective clinical studies tailoring treatment regimens to specific tumor molecular subtypes in UC and other indications.

  Study EGAS50000000497

• Plasma Nucleosome Profiling Reports on Tumor Burden and Molecular Subtypes in Small Cell Lung Cancer

  Small cell lung cancer (SCLC) is an aggressive malignancy with dismal prognosis and marked transcriptional heterogeneity that drives distinct therapeutic vulnerabilities. The clinical translation of these molecular insights is limited by limited access to tumor biopsies. Here, we apply chromatin immunoprecipitation of cell-free nucleosomes carrying active histone modifications followed by sequencing (cfChIP-seq) to 441 plasma samples from individuals with advanced SCLC, other neuroendocrine carcinomas (NEC), non-SCLC cancers, and healthy controls. cfChIP-seq faithfully captured the epigenetic and transcriptional landscape of tumor-derived cfDNA, including SCLC tissue/cell-of-origin signatures, and yielded a quantitative score of tumor fraction that tracked radiographic burden and prognosis. Integrating plasma cfChIP-seq with matched tumor transcriptomes (n = 73, including 41 time-matched pairs), we show that cfChIP-seq levels at promoters of lineage-defining transcription factors (ASCL1, NEUROD1, POU2F3, and ATOH1) correlate strongly with tumor RNA and support noninvasive inference of SCLC transcriptional subtypes directly from plasma. These findings establish cfChIP-seq as a practical liquid-biopsy platform that reports real-time tumor state and subtype, enabling precision monitoring and laying the groundwork for subtype-informed therapeutic stratification in SCLC.

  Study EGAS50000001916

• Exploratory Biomarker Analysis Using ctDNA in an Investigator-Initiated Trial of Alectinib for Rare Cancers Harboring ALK Alterations

  We performed targeted sequencing analysis of cfDNA from plasma collected before and after study treatment, together with matched normal DNA from peripheral blood cells, in patients enrolled in an investigator-initiated clinical trial of alectinib for rare cancers harboring ALK alterations. This study aims to identify biomarkers associated with the clinical efficacy of alectinib.

  Study JGAS000958

• Liquid Biopsy-informed Precision Oncology Study to Evaluate the Clinical Utility of Non-invasive Genomic Profiling for Cancer Treatment Selection

  DAC for EGA study: "Liquid Biopsy-informed Precision Oncology Study to Evaluate the Clinical Utility of  Non-invasive Genomic Profiling for Cancer Treatment Selection".

  Dac EGAC50000001165

• Nanopore Amplicon Sequencing data of 33 patient tumor and one primary cell line samples - all uveal melanoma

  Nanopore Amplicon Sequencing data of 4 amplicons in the GNA11, GNAQ, SF3B1 and SRSF2 genes in 33 uveal melanoma patient tumor samples and one primary cell line sample. Sequencing was performed on a MinION platform (Mk1B) using the SQK-RBK114.24 kit multiplexing 24 samples per flow cell. Basecalling was performed using the dna_r10.4.1_e8.2_400bps_sup@v4.3.0 model and dorado v.0.6.2.

  Study EGAS50000002137

• Liquid Biopsy-informed Precision Oncology Study to Evaluate the Clinical Utility of Non-invasive Genomic Profiling for Cancer Treatment Selection

  This dataset pertains to the first planned analysis of an observational trial assessing the clinical utility of serial LB, combined with precision oncology recommendations by a molecular tumor board (MTB). Serial LBs utilized a clinically validated 33-gene panel next-generation sequencing (NGS) assay. Key eligibility criteria included age≥18years, ECOG performance status 0-1, and advanced/metastatic solid tumors with progression on ≥1 lines of therapy. 50 patients were enrolled between March 2023 and July 2024.

  Study EGAS50000002145

• Evolutionary dynamics in the decades preceding acute myeloid leukaemia

  Somatic evolution in ageing tissues underlies many cancers, yet the quantitative rules governing pre-cancerous evolution remain incompletely understood. This study exploits a collection of serial blood serum samples from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), collected annually from as early as 15 years before a diagnosis of acute myeloid leukaemia (AML), to provide a quantitative description of pre-cancerous evolutionary dynamics. Longitudinal samples from women who subsequently developed AML, alongside timepoint-matched samples from age-matched cancer-free controls, were sequenced using TETRIS-seq, a deep duplex error-corrected sequencing approach covering a custom panel of single-nucleotide variants and indels, mosaic chromosomal alterations, and chromosomal rearrangements associated with clonal haematopoiesis and AML. Combined with evolutionary modelling, these data quantify the acquisition ages and fitness effects of key driver events in AML development, characterise the clonal dynamics that precede diagnosis, and show that pre-leukaemic evolution is consistent with a small set of evolutionary rules balancing chance and determinism. The deposited data comprise raw paired-end FASTQ files for all sequenced samples.

  Study EGAS50000002168

• MDSMPN_Rearrangement_Screen

  Genomic libraries (500 bps) will be generated from total genomic DNA derived from 11 Myelodysplastic Myeloproliferative neoplasms (MDSMPN) and subjected to total of two lanes of 50 bp, paired end sequencing on the llumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.

  Study EGAS00001000034

• 1__Fanconi_Anemia_transformation_to_AML

  Genomic libraries (500 bps) will be generated from total genomic DNA derived from 7 Fanconi anemia (FA) derived Acute myeloid leukemia samples and subjected to total of two lanes of 50 bp, paired end sequencing on the llumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.

  Study EGAS00001000033

• Metastatic_Prostate_Follow_Up_2

  Validation/deeper sequencing for metastatic prostate cancer samples

  Study EGAS00001000756

• Integrative_Oncogenomics_of_Multiple_Myeloma

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from Multiple Myeloma patient DNA and matched normal DNA from the same patients. Two lanes of Illumina GA sequencing will be performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.

  Study EGAS00001000036

• Gastric_and_Esophageal_tumour_rearrangement_screen

  Genomic libraries (500 bps) will be generated from total genomic DNA derived from gastric and esophageal tumours and subjected to total of two lanes of 50 bp, paired end sequencing on the llumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.

  Study EGAS00001000037

• Chugai_colorectal_organoid_sequencing

  Genomic and transcriptomic characterization of drug-resistant colon cancer stem cell lines.

  Study EGAS00001000872

• Chondrosarcoma_Exome_

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from Chondrosarcoma cancer and matched normal DNA from the same patients. Next Generation sequencing will be performed on the resulting exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes

  Study EGAS00001000038

• HER2_positive_Breast_Cancer_

  We propose to definitively characterise the somatic genetics of HER2+ve breast cancer through generation of comprehensive catalogues of somatic mutations in a number of cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.

  Study EGAS00001000042

• Analysis_of_genomic_integrity_of_disease_corrected_human_induced_pluripotent_stem_cells_by_exome_sequencing

  Induced pluripotent stem (iPS) cells hold great promise for autologous cell transplantation. In order to apply this therapy to monogenic disorder, disease-causing mutations must be corrected prior to transplantation. We generated iPS cells from patients with alpha-1 antitrypsin deficiency, which is caused by homozygous non-synonymous mutation in the SERPINA1 gene. In vitro differentiation of patient-derived iPS cells to hepatocytes showed recapitulation of the disease phenotype. We corrected the mutations by gene targeting using zinc finger nuclease (ZFN) and piggyBac transposon technologies. Our mutation correction is highly accurate. There is no exogenous sequence left behind at the targeted site. The corrected iPS cell-derived hepatocytes were indistinguishable from healthy hepatocyte, suggesting that the corrected gene was fully functional. The genomic integrity was also analyzed by CGH and SNP array, showing no genomic alterations. These are important points to ensure clinical safety as well as functional restoration of the corrected gene. One remaining question is if these corrected iPS cells are clinically safe at the single base-pair level. Recent publications suggested that cancer-related mutations are significantly accumulated during iPS cell propagation. We aim to assess the clinical safety of the corrected iPS cells by using exome sequencing. Outcome from this project would bring iPS cell technology one step closer to clinical applications.

  Study EGAS00001000055

• MPN_Genomes_validation_and_interim_samples

  MPN genome variant validation and interrogation of interim timepoints.

  Study EGAS00001000766

• Acute_Lymphoblastic_Leukemia_Sequencing

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 Acute Lymphoblastic Leukemia samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped build 37 of the human reference genome to facilitate the identification of novel cancer genes. In addition, 500bp, NO_PCR total genomic libraries will be prepared from the same samples and five lanes of Illumina GA sequencing will be analysed to characterise genome wide, somatically acquired structural variation.

  Study EGAS00001000058

• Epi_Tax_targeted_sequencing

  Sequencing of 350 cancer genes in BC samples from patients treated with either Epirubicin or Paclitaxel monotherapy in the neoadjuvant setting.

  Study EGAS00001000587

• Genentech Small Cell Lung Cancer (SCLC) Screen

  Exome capture, RNA-Seq, whole genome sequencing of set of Small Cell Lung Cancer samples.

  Study EGAS00001000334

• Angiosarcoma_whole_exome

  Extension of angiosarcoma whole genome sequencing study

  Study EGAS00001000588

• Screening_for_human_epigenetic_variation_at_CpG_islands

  Many human characteristics, including susceptibility to disease, are determined genetically. An unexplored alternative to such genetic determination concerns epigenetic mechanisms such as DNA methylation. CpG islands (CGIs) are generally constitutively hypomethylated, however there are circumstances in which they become heavily methylated and, when coincident with a gene promoter, this invariably causes transcriptional silencing. CGI methylation occurs in normal tissues during processes such as X-inactivation, but abnormal patterns of methylation have also been implicated in disease. The vast majority of evidence relates to cancer, where silencing of multiple genes in this way appears to be a causal contributor to the cancer state. To address the role and extent of CGI methylation in ‘normal’ and diseased cells we applied MBD-affinity purification in conjunction with next generation sequencing in a panel of human brain autopsy samples. These samples represent a panel of individuals as well as specific brain regions and neurological pathologies.

  Study EGAS00001000074

• Screening_for_abnormal_CGI_methylation_in_primary_colorectal_tumours

  A common hallmark of neoplastic cells is abnormal acquisition of CpG island (CGI) methylation and the silencing of associated gene promoters. To determine the extent and distribution of CGI methylation in colorectal cancer, we solexa sequenced MBD affinity purified DNA prepared from five colorectal tumours and matched colon mucosa from the same individuals.

  Study EGAS00001000076

• Human_Colorectal_Cancer_Exome_Sequencing

  In this experiment we sequenced a collection of genes identified as being mutated in a Sleeping Beauty Screen in a mouse colorectal Cancer Model in human tumours collected from patients with germline mutations in APC and also other familial CRC predisposition syndromes. We also sequenced the germline of these patients allowing us to identify somatically mutated genes. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001000077

• RNAseq_of_patients_with_Ewings_sarcoma

  Cancer is driven my mutations in the genome. We will uncover the mutations that give rise to Ewing’s sarcoma, a bone tumour that largely affects children. We will use second generation Illumina massively parallel sequencing, and bespoke software, to characterise the genomes and transcriptomes of Ewings’ sarcoma tumours.

  Study EGAS00001000267