15176 results for "cancer studies using rna-seq"

in 23.99 milliseconds.

• ATAC-Seq and CTCF ChIP-Seq on the OCIAML-2 cell line

  Study EGAS00001004741

• RNA sequencing of lung fibroblasts

  RNA sequencing of lung fibroblasts

  Study EGAS00001007857

• Characterization of four subtypes in morphologically normal tissue excised proximal and distal to breast cancer

  Our study provides insight into molecular alterations in HN tissues within the affected breast and offers a greater understanding of the spatial implications of these aberrations. This was achieved by performing a comprehensive analysis of RNA sequencing data and proteomic profiles from breast cancers (n=19) and their matched HN tissues (n=38), healthy breast from cosmetic reduction mammoplasty (RM; n=5), and risk reducing mastectomies (RR, n=5), with peritumoral samples excised at proximal (TP, <2 cm) and distal (TD, 5-10 cm) sites from the primary tumor.

  Study EGAS00001004510

• Molecular Evolution of Cancer

  Recently developed methods that utilize partitioning of long genomic DNA fragments, and barcoding of shorter fragments derived from them, have succeeded in retaining long-range information in short sequencing reads. These so-called read cloud approaches represent a powerful, accurate, and cost-effective alternative to single-molecule long-read sequencing. We developed software, GROC-SVs, that takes advantage of read clouds for structural variant detection and assembly. We apply the method to two 10x Genomics data sets, one chromothriptic sarcoma with several spatially separated samples, and one breast cancer cell line, all Illumina-sequenced to high coverage. Comparison to short-fragment data from the same samples, and validation by mate-pair data from a subset of the sarcoma samples, demonstrate substantial improvement in specificity of breakpoint detection compared to short-fragment sequencing, at comparable sensitivity, and vice versa. The embedded long-range information also facilitates sequence assembly of a large fraction of the breakpoints; importantly, consecutive breakpoints that are closer than the average length of the input DNA molecules can be assembled together and their order and arrangement reconstructed, with some events exhibiting remarkable complexity. These features facilitated an analysis of the structural evolution of the sarcoma. In the chromothripsis, rearrangements occurred before copy number amplifications, and using the phylogenetic tree built from point mutation data, we show that single nucleotide variants and structural variants are not correlated. We predict significant future advances in structural variant science using 10x data analyzed with GROC-SVs and other read cloud-specific methods.

  Study phs001255

• Efficacy of two different FGFR-inhibitors in a patient with extrahepatic cholangiocarcinoma harboring an FGFR2 mutation

  Cholangiocarcinomas (CCAs) is a type of cancer with few effective systemic therapies. Elucidation of the molecular landscape of the disease from genomic studies based on next generation sequencing (NGS) has contributed to the introduction of new targeted therapies. One of these treatments consists of a class of small molecules that target members of the FGFR family of receptor tyrosine kinases. These drugs are effective and have been approved for cholangiocarcinomas with fusions or rearrangements of FGFR genes. In contrast, the role of these inhibitors in cholangiocarcinomas with mutations in FGFR genes is less well defined. We report here a patient with a cholangiocarcinoma bearing a FGFR2 p.Ser252Trp mutation. The patient was treated with two different FGFR inhibitors, as the first caused ocular toxicity. She obtained clinical benefit from both. This case illustrates the efficacy of FGFR inhibitors on cholangiocarcinoma with specific point mutations. This is the first case to report the clinical benefit of these drugs in FGFR2 p.Ser252Trp mutation. Clinical benefit can be sustained, as seen in our patient. Our case also shows that FGFR inhibitors-induced adverse effects, such as ocular toxicities, may not recur after re-challenge with an alternative drug of the same class.

  Dataset EGAD50000000021

• Clonal selection after gene therapy in sickle cell disease

  While gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD), the occurrence of myeloid malignancies in clinical trials has prompted concern. To interrogate potential mechanisms underlying increased cancer risk, we used hematopoietic stem cell (HSC) clonal tracking by whole genome sequencing (WGS) to map the somatic mutation and clonal landscape of 2,592 gene modified as well as unmodified single stem and progenitor cells from six SCD patients undergoing gene therapy (7-26 years old, average 12.7× depth). Pre-GT phylogenetic trees in SCD were highly polyclonal and mutation burdens per cell were elevated in some, but not all, patients. Post-GT, no clonal expansions were identified. However, an increased frequency of driver mutations associated with myeloid neoplasms or clonal hematopoiesis (DNMT3A- and EZH2-mutated clones in particular) were seen in both genetically modified and unmodified cells suggested positive selection of mutant clones during gene therapy. This work sheds light on the mutation landscape and HSC clonal dynamics in gene therapy for SCD and highlights enhanced fitness of some HSCs harboring pre-existing driver mutations following gene therapy. Future studies should define the long-term fate of mutant clones including any contribution to expansions associated with myeloid neoplasms.

  Dataset EGAD00001010914

• Gabriella Miller Kids First (GMKF) Pediatric Research Program in Susceptibility to Ewing Sarcoma Based on Germline Risk and Familial History of Cancer

  Ewing sarcoma (EWS) is a deadly bone cancer that occurs in children and adolescents. Mounting evidence suggests that a genetic predisposition exists for this pediatric cancer, although the specific genetic contribution has yet to be identified. EWS has never been linked to a specific cancer predisposition syndrome, although several case reports have been published that describe siblings and cousins with EWS. Furthermore, neuroectodermal tumors appear to occur more commonly in families with EWS. The two consistent epidemiology findings in EWS include a very strong Caucasian predilection and increased rates of hernia in EWS patients and their family members. Finally, the role of genetic microsatellite repeats in EWS tumorigenesis has been recently described, and these GGAA microsatellites are polymorphic in repeat size and location across the genome. The study goals of this Kids First project include (1) To identify cancer predisposition genes in EWS trios increasing disease risk, (2) To identify genome-wide GGAA microsatellite repeats in EWS trios increasing disease risk, and (3) To identity de novo mutation and structural variant rates in EWS trios reflecting underlying DNA repair defects that increase disease risk. As part of the Kids First Common Fund initiative, this study proposal will further elucidate the genetic contribution to pediatric cancer development. Around 375 of these trios were selected for whole genome sequencing as part of the Gabriella Miller Kids First fund. The EWS trios have been collected as part of the Children's Oncology Group's AEPI10N5 Study ("Genetic Epidemiology of Ewing Sarcoma"), and each trio has associated phenotypic data including a detailed family history. We will interrogate the sequence data using our genomic analysis pipeline at the University of Utah and the Utah Science Technology and Research initiative's (USTAR) Center for Genetic Discovery. We will look for the genetic contribution to EWS and the sequence data with be shared in a repository designated by the Kids First Common Fund. The WGS of these ~375 EWS trios will help us to understand the genetic origins of a deadly childhood cancer and may lead to novel strategies for prevention and treatment.

  Study phs001228

• RNA-sequencing of ex situ stimulated donors blood cells

  Cells from whole blood stimulation assay were cryopreserved. The cryopreserved cells were thawed and subjected to RNA preparation. RNA obtained were subjected to for bulk sequencing.

  Study EGAS50000001077

• H3K27Ac ChIP-seq of 9 cHL cell lines

  The dataset contains 36 ChIP-seq data for H3K27Ac and their corresponging inputs for 9 cHL cell lines. Data are raw paired-end fasq files for each histone and input, and for each cell line.

  Dataset EGAD50000001272

• The Transcriptional Landscape of SHH Medulloblastoma

  To further understand the biology of Sonic hedgehog medulloblastoma and its molecular subtypes, we studied 250 human Shh-MB using strand-specific RNA sequencing. We identified novel alterations within the cAMP dependent pathway and found that 18% of tumors have genetic events that directly target the abundance and/or stability of MYCN. We also discovered an extensive network of fusions in focally amplified regions, and several loss-of-function fusions in tumor suppressor genes PTCH, SUFU and NCOR1. Molecular convergence on a core of specific genes by nucleotide variants, copy number aberrations, and gene fusions highlights key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma.

  Dataset EGAD00001006305