11769 results for "cancer rna-seq"

in 14.75 milliseconds.

• The Genomic Landscape of Response to EGFR Blockade in Colorectal Cancer

  Colorectal cancer (CRC) is the third most common cancer world-wide with 1.2 million patients diagnosed yearly. In late stage CRC, the most commonly used targeted therapies are monoclonal antibodies cetuximab and panitumumab, which inactivate EGFR. Recent studies have identified alterations in KRAS and other genes as likely mechanisms of primary and secondary resistance to anti-EGFR antibody therapy. Despite these efforts, additional mechanisms of resistance to EGFR blockade are thought to be present in CRC and little is known about determinants of sensitivity to this therapy. To examine the effect of somatic genetic changes in CRC on response to anti-EGFR antibody therapy, we performed complete exome sequence and copy number analyses of 129 patient-derived tumorgrafts and targeted genomic analyses of 55 patient tumors, all of which were KRAS wild-type. We analyzed the response of tumors to anti-EGFR antibody blockade in tumorgraft models or in clinical settings. In addition to previously identified genes, we detected mutations in ERBB2, EGFR, FGFR1, PDGFRA, and MAP2K1 as potential mechanisms of primary resistance to this therapy. Novel alterations in the ectodomain of EGFR were identified in patients with acquired resistance to EGFR blockade. Amplifications and sequence changes in the tyrosine kinase receptor adaptor gene IRS2 were identified in tumors with increased sensitivity to anti-EGFR therapy. Therapeutic resistance to EGFR blockade could be overcome in tumorgraft models through combinatorial therapies targeting actionable genes. These analyses provide a systematic approach to evaluate response to targeted therapies in human cancer, highlight new mechanisms of responsiveness to anti-EGFR therapies, and provide new avenues for intervention in the management of CRC.

  Study EGAS00001001305

• Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing

  Background Single-cell micro-metastases of solid tumors often occur in the bone marrow. These disseminated tumor cells (DTCs) may resist therapy and lay dormant or progress to cause overt bone and visceral metastases. The molecular nature of DTCs remains elusive, as well as when and from where in the tumor they originate. Here, we apply single-cell sequencing to identify and trace the origin of DTCs in breast cancer. Results We sequence the genomes of 63 single cells isolated from six non-metastatic breast cancer patients. By comparing the cells DNA copy number aberration (CNA) landscapes with those of the primary tumors and lymph node metastasis, we establish that 53% of the single cells morphologically classified as tumor cells are DTCs disseminating from the observed tumor. The remaining cells represent either non-aberrant ‘normal’ cells or aberrant cells of unknown origin that have CNA landscapes discordant from the tumor. Further analyses suggest that the prevalence of aberrant cells of unknown origin is age-dependent, and that at least a subset is hematopoietic in origin. Evolutionary reconstruction analysis of bulk tumor and DTC genomes enables ordering of CNA events in molecular pseudo-time and traced the origin of the DTCs to either the main tumor clone, primary tumor subclones, or subclones in an axillary lymph node metastasis. Conclusions Single-cell sequencing of bone marrow epithelial-like cells, in parallel with intra-tumor genetic heterogeneity profiling from bulk DNA, is a powerful approach to identify and study DTCs, yielding insight into metastatic processes. A heterogeneous population of CNA-positive cells is present in the bone marrow of non-metastatic breast cancer patients, only part of which are derived from the observed tumor lineages.

  Study EGAS00001002102

• 'Targeted High Throughput Sequencing in Clinical Cancer Settings: Formaldehyde fixed-paraffin embedded (FFPE) tumor tissues, input amount and tumor heterogeneity'

  "Background: Massively parallel sequencing technologies have brought an enormous increase in sequencing throughput. However, these technologies need to be further improved with regard to reproducibility and applicability to clinical samples and settings. Methods: Using identification of genetic variations in prostate cancer as an example we address three crucial challenges in the field of targeted re-sequencing: Small nucleotide variation (SNV) detection in samples of formalin-fixed paraffin embedded (FFPE) tissue material, minimal amount of input sample and sampling in view of tissue heterogeneity.Results: We show that FFPE tissue material can supplement for fresh frozen tissues for the detection of SNVs and that solution-based enrichment experiments can be accomplished with small amounts of DNA with only minimal effects on enrichment uniformity and data variance. Finally, we address the question whether the heterogeneity of a tumor is reflected by different genetic alterations, e.g. different foci of a tumor display different genomic patterns. We show that the tumor heterogeneity plays an important role for the detection of copy number variations, but is of minor importance for the detection of somatic variations.Conclusions: The application of high throughput sequencing technologies in cancer genomics opens up a new dimension for the identification of disease mechanisms. In particular the ability to use small amounts of FFPE samples available from surgical tumor resections and histopathological examinations facilitates the collection of precious tissue materials. However, care needs to be taken in regard to the locations of the biopsies taken, which can have an influence on the prediction of copy number variations. Bearing these technological challenges in mind will significantly improve many large-scale sequencing studies and will - on a long-range - result in a more reliable prediction of individual cancer therapies."

  Study EGAS00001000136

• Combining a Universal Telomerase Based Cancer Vaccine with Ipilimumab in Patients with Metastatic Melanoma - Five-year Follow up of a Phase I/IIa Trial

  Background Ipilimumab improves survival for patients with metastatic malignant melanoma. Combining a therapeutic cancer vaccine with ipilimumab may increase efficacy by providing enhanced anti-tumor immune responses. UV1 consists of three synthetic long peptides from human telomerase reverse transcriptase (hTERT). These peptides comprise epitopes recognized by T cells from cancer patients experiencing long-term survival following treatment with a first-generation hTERT vaccine, and generate long-lasting immune responses in cancer patients when used as monotherapy. The objective of this trial was to investigate the safety and efficacy of combining UV1 with ipilimumab in metastatic melanoma. Patients and methods In this phase I/IIa, single center trial [NCT02275416], patients with metastatic melanoma received repeated UV1 vaccinations, with GM-CSF as an adjuvant, in combination with ipilimumab. Patients were evaluated for safety, efficacy and immune response. Immune responses against vaccine peptides were monitored in peripheral blood by measuring antigen-specific proliferation and IFN-γ production. Results Twelve patients were recruited. Adverse events were mainly diarrhea, injection site reaction, pruritus, rash, nausea and fatigue. Ten patients showed a Th1 immune response to UV1 peptides, occurring early and after few vaccinations. Three patients obtained a partial response and one patient a complete response. Overall survival was 50% at 5 years. Conclusion Treatment was well tolerated. The rapid expansion of UV1-specific Th1 cells in the majority of patients indicates synergy between UV1 vaccine and CTLA-4 blockade. This may have translated into clinical benefit, encouraging the combination of UV1 vaccination with standard of care treatment regimes containing ipilimumab/CTLA-4 blocking antibodies.

  Study EGAS00001005253

• Integration of intra-sample contextual error modeling for improved detection of somatic mutations

  Study EGAS00001003806

• IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" Italian Cancer Center Data Access Committee

  Dac EGAC00001003223

• IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" Italian Cancer Center Data Access Committee

  Dac EGAC00001003227

• St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project Steering Committee

  Dac EGAC00001000045

• Data access policy for PDTX Breast Cancer data from Bruna et al (2016), Cell.

  Dac EGAC00001000540

• DAC for "A Functional Network of Gastric-Cancer-Associated Splicing Events Controlled by Dysregulated Splicing Factors"

  Dac EGAC00001000675

• DAC for study: "Circulating tumour DNA abundance and potential utility in de novo metastatic prostate cancer"

  Dac EGAC00001001099

• The University of Hong Kong Colon Cancer Organoids Genomics Study Data Access Committee

  Dac EGAC00001001405

• The data access committee for Detection and characterization of lung cancer using cell-free DNA fragmentomes

  Dac EGAC00001002184

• Treatment-mediated selection of lethal prostate cancer clones defined by copy number architectures

  Dac EGAC00001002865

• Whole exome sequencing of metastatic breast cancer

  Dataset EGAD00001000836

• Nanostring_nCounter_BreastCancer360

  hormone receptor-positive early breast cancer by Nanostring BC360 panel

  Dataset EGAD00010001994

• Cancer-Unknown-Primary-Array-Methylation-H021

  CUP samples using 850k

  Dataset EGAD00010002036

• The landscape of somatic mutations in epigenetic regulators across 1000 pediatric cancer genomes

  Study EGAS00001000449

• Identification of mutations and structural rearrangements in plasma DNA form metastatic prostate cancer patients

  Study EGAS00001000453

• Single cell sequencing: Capturing the origin and dynamics of chromosomal copy-number heterogeneity

  Study EGAS00001003812

• STM4 - Mouliere et al, 2018. Enhanced detection of circulating tumor DNA by fragment size analysis

  Study EGAS00001004418

• BRCA2, ATM, and CDK12 defects differentially shape prostate tumor driver genomics and clinical aggression

  Study EGAS00001004800

• IG-MYC rearrangement defines a high-risk subgroup of B-cell precursor acute lymphoblastic leukaemia

  Study EGAS00001005111

• Genomic Analysis of Focal Nodular Hyperplasia with Associated Hepatocellular Carcinoma Unveils its Malignant Potential

  Study EGAS00001005313

• Evaluating CRISPR-based Prime Editing for cancer modeling and CFTR repair in organoids

  Study EGAS00001005358