14983 results for "cancer studies using rna-seq"

in 20.89 milliseconds.

• "Single nucleotide variant detection in multiple foci of three prostate cancer tumors"

  "Single nucleotide variant detection in multiple foci of three prostate cancer tumors"

  Dataset EGAD00001000035

• "Copy number variant detection in multiple foci of three prostate cancer tumors"

  "Copy number variant detection in multiple foci of three prostate cancer tumors"

  Dataset EGAD00001000036

• WGS data of serially passaged TIC-enriched spheres of colorectal cancer

  WGS data of serially passaged TIC-enriched spheres of colorectal cancer

  Dataset EGAD00001006265

• Single cell sequencing of ovarian cancer

  Single cell sequencing of 12 ovarian cancer biopsies from 7 patients.

  Dataset EGAD00001006898

• Whole_genome_sequencing_of_rhabdomyosarcoma_tumouroids

  The aim of this study is to investigate the genomic landscape of human cancer.

  Study EGAS00001008270

• Whole_Genome_sequencing_of_rhabdomyosarcoma_tumour_tissue

  The aim of this study is to investigate the genomic landscape of human cancer.

  Study EGAS00001008274

• Investigation of a method for generating cells for regenerative medicine using comprehensive nucleic acid analysis of iPS cell-derived cardiomyocytes.

  Regenerative medicine for heart failure is expected to restore cardiac function by using human iPS cells (hiPSCs). In our laboratory, it was shown that transplantation of cardiomyocytes (CMs) derived from hiPSCs into a pig model of myocardial infarction improves the disease condition. However, the instability of differentiation efficiency and tumorigenicity after transplantation are still issues to be resolved. We attempt to identify and analyze the genes and DNA methylation associated with the induction of differentiation of hiPSCs into CMs with the aim of achieving stable induction of CMs differentiation. Furthermore, we aim to analyze genes involved in tumorigenesis in CMs, and to develop a predictive marker for tumorigenesis to ensure the safety of cells before transplantation.

  Study JGAS000665

• Genetics and therapeutic responses to TIL therapy of pancreatic cancer PDX models

  Pancreatic cancer is the 7th leading cause of cancer-related deaths worldwide. Checkpoint immunotherapy has not yet showed encouraging results in pancreatic cancer possibly owing to a poor immunogenicity and/or an immune suppressive microenvironment. The aim of this study was to develop patient-derived xenografts (PDX) models and to assess if autologous tumor-infiltrating lymphocytes (TILs) would have anti-tumoral activity in pancreatic cancer. Tumor biopsies from 29 patients were subcutaneously transplanted into NOG mice. Tumor growths were confirmed in 11 out of 29 transplantations. The PDX tumors histologically resembled their original biopsies, but since stromal cells in the PDX model tumors were from mouse, their gene expression differed from the original biopsies. Immune checkpoint ligands other than PD-L1 were expressed in pancreatic cancers but PD-L1 was rarely expressed. One of the three tumors that did express PD-L1 was an adenosquamous cancer and another had a mismatch repair deficiency. TILs were expanded from six tumors and were injected into NOG or human interleukin-2 transgenic-NOG (hIL2-NOG) mice carrying PDX tumors. Regression of tumors could be verified in hIL2-NOG mice in 3 of the 6 PDX models treated with autologous TILs, including the adenosquamous PDX model. In conclusion, PDX models of pancreatic cancer can be used to learn more about tumor characteristics and biomarkers, and to evaluate responses to ACT and combination therapies. The major benefit of the model is that modifications of T cells can be tested in an autologous humanized mouse model to gain preclinical data to support the initiation of a clinical trial.

  Study EGAS00001005596

• Frequent post-treatment monitoring of colorectal cancer using individualized ctDNA validated by multi-regional molecular profiling

  Purpose: Circulating tumor DNA (ctDNA) analysis has been proposed as an approach for prediction of post-treatment patient outcomes. However, whether a single platform will provide optimal information in all patients or alternatively a patient-specific monitoring approach based on assessment of mutations in the primary tumor from that patient remains an urgent question. Experimental Design: We conducted multiregional sequencing of 42 specimens of 14 colorectal tumors (Stage III and more) from 12 patients, including two double cancer cases, to identify the full spectrum of mutational heterogeneity and identify aberrations that could be used to develop personalized ctDNA assays. Results: ?Founder? mutations that occur in all regions of the sample were identified in 12/14 (85.7%) tumors. Subsequent phylogenetic analysis of each tumor showed that 12/14 tumors (85.7%) carried at least one ?truncal? mutation. Most founder and truncal mutations exhibited higher variant allele frequency (VAF) than ?non-founder? and ?branch? mutations. In addition, both founder and truncal mutations were more likely to be detected as ctDNA than non-founder and branch mutations. Synchronized ctDNA dynamics of multiple mutations suggested those mutations from the same clonal origin. For 10/12 patients (83.3%) with nearly 1,000 days of post-operative observation, the validity of frequent personalized ctDNA monitoring was confirmed in terms of early relapse prediction, treatment efficacy, and non-relapse corroboration. Conclusions: Personalized ctDNA monitoring based on aberrations with a high VAF in the primary tumor site should be explored in larger prospective clinical trials to determine the full clinical validity.

  Study JGAS000243

• Analysis of mutational and proteomic heterogeneity of gastric cancer to monitor post-treatment tumor burden using circulating tumor DNA

  It remains unclear whether complete spectrum of tumor heterogeneity is reflected in circulating tumor DNA (ctDNA). Here, we performed multi-regional target sequencing of primary tumors from 10 patients who underwent surgical resection for gastric cancer. A total of 126 non-synonymous mutations were identified from 30 samples from 10 tumors. Of these, 16 (12.7%) were likely mutations that occurred early in tumor development (i.e., present in all three regions) and were designated founder mutations. Among those validated with highly sensitive digital PCR (dPCR), 93% of non-founder mutations were found in all three regions. Variant allele frequencies (VAFs) of founder mutations were significantly higher than those of non-founder mutations. Phylogenetic analysis demonstrated that five of eight tumors (62.5%, excluding two hypermutator) had at least one identifiable truncal/founder mutation. These findings led us to prioritize founder mutations for ctDNA detection with individually-designed primer/probe sets for dPCR. Marked proteomic diversity was present across the tumor regions both within and between patients independent of mutational status. In preoperative plasma, the average ctDNA VAF of founder mutations was significantly higher than that of non-founder mutations (p = 0.039). Our present data demonstrated that high VAF mutations in the tumor likely represent founder or truncal mutations. However, mutation patterns alone appear insufficient to predict protein heterogeneity. These results suggest that, in practice, mutations having high VAF identified without multi-regional sequencing may be useful for ctDNA monitoring but are inadequate to fully predict proteomic heterogeneity of the tumor.

  Study JGAS000231

• Treatment stratification and biomarker validation using patient-derived head and neck cancer organoids

  Background Organoids are three-dimensional structures that can be grown from patient-derived material including carcinomas. These in vitro models can be cryopreserved to generate “living” biobanks that reflect patient heterogeneity. Head and neck cancer (HNC) is a collective term used for tumors arising in the head and neck area, including squamous cell carcinomas (HNSCC) and adenocarcinoma of the salivary gland. Methods to culture patient-derived HNC organoids have previously been described. Methods Organoids were derived from resection or biopsy material of patients included between 2016 and 2022. Organoids were characterised with immunohistochemistry and whole exome sequencing (WES) and exposed to chemo-, radio- and targeted-therapies. CRISPR/Cas9-based gene editing was applied to validate proposed biomarkers. Results We have extended our previously published organoid biobank to a total of 110 organoid models, some of which were characterised by histology and WES. Organoids recapitulated both single nucleotide variants and copy number alterations as found in patient HNSCC samples. Organoid and patient response to radiotherapy (RT; primary (n=6) and adjuvant (n=15)) could be compared in 21 HNC cases. In the adjuvant RT group, organoids derived from patients that relapsed were more resistant to RT in vitro, showing potential for guiding treatment options in this subset of patients. Conclusion Taken together, these results indicate illustrate the potential of organoids as a diagnostic tool in personalised medicine for HNC and indicate the potential of this technology for biomarker discovery and validation within the context of relevant patient heterogeneity.

  Study EGAS00001007076

• Hereditary Cancer Predisposition Syndromes and Uveal Melanoma

  Uveal melanoma (UM) is a subtype of melanoma characterized by the strong contribution of genetic rather than environmental factors in the pathogenesis of the disease, making it an ideal model disease to study the genetic basis of cancer. The long-term goal of our laboratory is to determine the genes and mechanisms responsible for hereditary cancer predisposition associated with UM. BAP1 has been identified as a candidate gene with definitive association with predisposition to UM. However, pathogenic variants in BAP1 are detected in only a small subset of UM patients even those with strong personal and family history of cancer suggesting the existence of other candidate genes. The goal of this project is to identify novel candidate genes contributing to hereditary predisposition to UM in patients with no detectable germline pathogenic variant in BAP1.

  Study phs001943

• Evolutionary Origins of Recurrent Pancreatic Cancer

  Surgery is the only curative option for patients with Stage I/II pancreatic cancer, nonetheless most patients will recur after surgery and die of their disease. To identify novel opportunities for management of recurrent pancreatic cancer we performed whole exome or targeted sequencing of 10 resected primary cancers and their matched intrapancreatic recurrences or distant metastases. We identified that recurrent disease develops from a monophyletic or polyphyletic origin, and this distinction has potential clinical relevance. In all patients, treatment induced genetic bottlenecks led to a modified genetic landscape and subclonal heterogeneity for driver gene alterations in part due to intermetastatic seeding. In one patient what was believed to be recurrent disease was an independent (second) primary tumor. These findings strongly advocate for routine post-treatment sampling in the management of recurrent pancreatic cancer.

  Study EGAS00001004097

• WGS of liver cancer in the Japanese population

  Hepatocellular carcinoma (HCC) is the third leading cancer-related cause of death and the seventh most common form of cancer worldwide, with an estimate of more than 700,000 new cases each year. The most established risk factors of HCC are chronic HBV and HCV infection. HBV infection is responsible for over 50% of the worldwide attributable risk of HCC, especially in East Asia and Africa, while in Japan and several Western countries HCV infection is the most common risk factor for HCC. To gain insights into the molecular alterations of virus-associated HCC, we performed whole genome sequencing (WGS) of 321 HCC tumors from 159 patients. This work was performed as a part of the ICGC (International Cancer Genome Consortium) project.

  Study EGAS00001000678

• The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer

  Reactivation of telomerase reverse transcriptase (TERT) expression enables cells to overcome replicative senescence and escape apoptosis, fundamental steps in the initiation of human cancer. Multiple cancer types, including up to 83% of glioblastomas (GBM), harbor highly recurrent TERT promoter mutations of unknown function but specific to two nucleotide positions. We identify the functional consequence of these mutations in GBM to be recruitment of the multimeric GABP transcription factor specifically to the mutant promoter. Allelic recruitment of GABP is consistently observed across four cancer types, highlighting a shared mechanism underlying TERT reactivation. Tandem flanking native ETS motifs critically cooperate with these mutations to activate TERT, likely by facilitating GABP heterotetramer binding. GABP thus directly links TERT promoter mutations to aberrant expression in multiple cancers.

  Study EGAS00001001242

• PanCuRx Translational Research Initiative

  The goal of the PanCuRx TRI is to seek solutions to the high fatality rate of pancreatic adenocarcinoma (PDAC), the most common type of pancreatic cancer, by generating new knowledge about the genetics and biology of the disease, mechanisms of how tumours grow and tailored treatment options. PDAC is the fourth leading cause of cancer death in Canada and is expected to become the second-leading cause of cancer death within the next decade. The current five-year survival rate of eight per cent is the lowest of all epithelial cancers. There are major clinical challenges to treating the disease, including the fact that PDAC spreads to other parts of the body early so surgical removal of the tumour benefits few patients, that PDAC has proven relatively resistant to systemic therapies such as chemotherapy and that there has been limited benefit from the use of newer molecular targeted agents. The PanCuRx team has created the world’s first resource of tumour-purified PDAC whole genomes; more than 500 PDAC samples, with combined clinical annotation, have been successfully sequenced and analyzed at the Ontario Institute for Cancer research in Toronto. The resulting clinical genomic resource created from this data has led to multiple new findings that have established a framework to better understand PDAC biology and lays the foundation for new genomic approaches to better understanding the disease. The team also launched a clinical trial called COMPASS (Comprehensive Molecular Characterization of Advanced Ductal Pancreas Adenocarcinoma for Better Treatment Selection: A Prospective Study), which is recruiting patients with advanced PDAC (both locally advanced and metastatic) at The Princess Margaret Cancer Centre (PM) in Toronto. The study uses the molecular results from individual patient tumours to guide selection of better second line treatment on a case-by-case basis. The primary objective of the initial study was to assess the feasibility of collecting tumour materials from patients with advanced PDAC and delivering results within 56 days of biopsy. Having achieved this objective, the trial has expanded to other cancer centres across Canada. Pancreatic cancer is one of the most deadly forms of cancer and outcomes have not improved in four decades. The PanCuRx initiative is providing a better understanding of the disease and actively applying new knowledge to cancer patients through clinical trials. This knowledge will help to improve quality of life and prolong survival for pancreatic cancer patients worldwide.

  Study EGAS00001002543

• Scalable ultra-high-throughput multiplexed single-cell chromatin and RNA profiling reveals gene regulatory dynamics during stimulation time courses and CRISPR perturbation screens

  Data for 1) hiPSC-derived macrophages across a polarization time course from the naive M0-state to the M1- and M2-states, 2) Primary T-cells differentiated to helper subtypes, and 3) spontaneous differentiation of hiPSCs upon perturbation of GATA2, NR4A2 or SOX17

  Dac EGAC50000000485

• Waldenström Macroglobulinemia Single-Cell Data Access Committee

  This Data Access Committee (DAC) is responsible for reviewing and approving access requests for controlled-access human single-cell sequencing data, including single-cell RNA sequencing and immune receptor profiling, generated from patients with Waldenström macroglobulinemia. The DAC ensures that all data access requests comply with the informed consent provided by study participants and are consistent with applicable ethical and regulatory requirements.

  Dac EGAC50000000863

• 20190219_EGA_MelanomaOnTreatment

  Illumina platform sequencing data for matched tumour-normal DNA samples from 77 melanoma patients participating in a study investigating response to immunotherapy. Selected cases also have RNA sequencing of the tumour.

  Dataset EGAD00001004869