14444 results for ""Pennsylvania+German"+ACS+study+'Socius'+open+access"

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• Spatiotemporal single-cell analysis reveals a time-dependent immunological modulation by multi-fractionated radiotherapy in esophageal cancer

  Description Here, by integrative spatial and single-cell analyses using spatial transcriptome (VISIUM) and single-cell RNA sequencing (scRNA-seq), we examined the spatiotemporal dynamics of immune-response in the tumor microenvironment of esophageal squamous cell carcinoma (ESCC) before, during and after RT. The comprehensive single-cell analyses demonstrated the infiltration of immune cells into tumor with the dynamic change of immune-stimulatory and -suppressive gene expression after RT. ScRNA-seq analysis uncovered the time- and cell-type-dependent alteration of gene expression profile from during to after RT. This datasets in the present study will provide the information of RT-induced gene signature to seek an appropriate target of personalized immunotherapy combined with radiotherapy and of determining the timing of the combination therapy.

  Study JGAS000712

• Establishment and Genomic Validation of Novel Patient-Derived Xenograft Models for Drug Discovery in Gastrointestinal Stromal Tumor

  This dataset contains targeted next-generation sequencing data generated with the Illumina TruSight Oncology 500 (TSO500) assay from six gastrointestinal stromal tumors (GIST) and matched patient-derived xenograft (PDX) models established at Fox Chase Cancer Center (Philadelphia, PA). GIST are most commonly driven by activating mutations in KIT or PDGFRA, and this study focused on KIT-mutant tumors. All PDXs were derived from metastatic patient tumors previously treated with one or more tyrosine kinase inhibitors (TKIs). PDXs were maintained through series of passages and represents in vivo models of differential TKI sensitivity. The dataset represents a detailed comparison of mutational profiles between primary tumors and corresponding PDXs across passages, enabling studies of genomic stability, resistance mechanisms, and the evaluation of novel therapeutic strategies in GIST.

  Study phs004185

• RNA sequencing data from glioblastoma primary cell lines treated with indisulam

  This study aimed to develop NovumRNA, a bioinformatics pipeline designed to predict non-canonical tumor-specific antigens (ncTSAs) from human tumor RNA-sequencing data, potentially broadening the target pool for cancer neo-epitope-based immunotherapies. The splicing-modulating drug indisulam was investigated for its potential to induce aberrant transcriptomes, potentially increasing ncTSAs, subsequently predicted by NovumRNA. Four glioblastoma primary cell lines were derived from patient Cavitron Ultrasonic Aspirator (CUSA) material, cultured as neurospheres, and treated with indisulam or vehicle control. RNA was extracted at 6 and 16 hours post-treatment and sequenced using the NovaSeq platform. The resulting RNA-seq data was analyzed with NovumRNA, using healthy brain GTEx samples as controls, to identify and validate ncTSAs induced by indisulam treatment. NovumRNA is available at: https://github.com/ComputationalBiomedicineGroup/NovumRNA.

  Study EGAS50000000680

• ECM-free patient-derived organoids preserve diverse prostate cancer lineages and uncover in vitro-enriched cell types

  Patient-derived organoids (PDOs) hold promise for modeling various cancers, yet their application in prostate cancer (PCa) has been limited due to low culture success and the predominance of non-tumor-like cells. Using 164 PCa samples and optimizing culture conditions, we demonstrate that an extracellular matrix (ECM)-free culture method improves PDO take-rates, fostering cell populations with luminal and PCa-specific characteristics. Single-cell RNA sequencing (scRNA-seq) reveals that these ECM-free PDOs closely mirror their original tumors at the transcriptomic level and maintain a diverse array of tumor cell types, unlike traditional Matrigel-based cultures which predominantly yield benign-like cells. This study introduces a PCa PDO single-cell atlas, providing a valuable resource for advancing prostate cancer research.

  Study EGAS50000000807

• Spatially resolved single-nucleus RNA sequencing of Choroid Plexus Tumours reveals clinically relevant hypoxia- and stress-driven dedifferentiation programs that sculpt an immunosuppressive and pro-angiogenic microenvironment

  Our study leverages single-nucleus RNA sequencing (~124,500 nuclei) and spatial transcriptomics (~40,650 spots) to dissect the molecular architecture of CPTs. We generated a comprehensive transcriptomic atlas of 45 CPT samples spanning all three methylation groups and a reference cohort of 16 non-neoplastic choroid plexus (ChP) samples, spanning foetal, paediatric and adult specimens. Key discoveries from this investigation include that paediatric B tumorus exhibit a dedifferentiated state and enrichment of stress-related metaprograms, including hypoxia, TGFß signaling, Interferon I signaling and early stress response, that correlate with poor clinical outcome and antagonise multiciliogenesis. On a spatial level, these stress-linked programs co-localise with immunosuppressive, pro-angiogenic microenvironment, suggesting a link between developmental arrest, microenvironmental remodelling and aggressive behaviour.

  Study EGAS50000001617

• High-depth whole genome sequencing of 26 premalignant breast lesions

  Ductal carcinoma in situ (DCIS) is a non-obligate precursor lesion of breast cancer, representing 20-25% of newly diagnosed breast cancer lesions. It is currently not possible to predict which DCIS patients will progress to invasive breast cancer. The samples deposited here are part of a larger study using high-depth whole-genome sequencing (WGS) to investigate the somatic mutation genomic landscape of DCIS. Comprehensive evaluation of DCIS genomes aims to uncover biological insights into breast cancer progression and potential opportunities to stratify DCIS patients for personalised treatment options or active surveillance. Due to specific restrictions imposed by the ethical approval at sample collection, the use of the germline data is restricted to filtering of somatic mutation calls only and cannot be used outside this purpose.

  Study EGAS50000001559

• Multiregional sequencing of IDH-WT glioblastoma reveals high genetic heterogeneity and a dynamic evolutionary history

  Glioblastoma is the most common and aggressive primary brain malignancy in adults. In addi-tion to extensive inter-patient heterogeneity, glioblastoma shows intra-tumor extensive cellular and molecular heterogeneity, both spatially and temporally. This heterogeneity is one of the main reasons for the poor prognosis and overall survival. Moreover, it raises the important question of whether the molecular characterization of a single bioptic sample, as performed in standard di-agnostics, actually represents the entire lesion. In this study, we sequenced the whole-exome of nine spatially different cancer regions of three primary glioblastomas. We characterized their mutational profiles and copy number alterations, with implications for our understanding of tu-mor biology in relation to clonal architecture and evolutionary dynamics, as well as therapeuti-cally relevant alterations.

  Study EGAS00001005128

• XClone for analyzing somatic copy number alterations

  Somatic copy number alterations (CNAs) are major mutations that contribute to the development and progression of various cancers. Despite a few computational methods proposed to detect CNAs from single-cell transcriptomic data, the technical sparsity of such data makes it challenging to identify allele-specific CNAs, particularly in complex clonal structures. In this study, we present a statistical method, XClone, that strengthens the signals of read depth and allelic imbalance by effective smoothing on cell neighborhood and gene coordinate graphs to detect haplotype-aware CNAs from scRNA-seq data. By applying XClone to multiple datasets with challenging compositions, we demonstrated its ability to robustly detect different types of allele-specific CNAs and potentially indicate whole genome duplication, therefore enabling the discovery of corresponding subclones and the dissection of their phenotypic impacts.

  Study EGAS00001007854

• Whole-exome sequencing of breast cancer metastasis and corresponding blood samples

  This study included samples from metastatic breast cancer patients who underwent a biopsy in the context of SAFIR01 (NCT01414933), SAFIR02 (NCT02299999), SHIVA (NCT01771458) and MOSCATO (NCT01566019) prospective trials. These French multicentre trials used high throughput genome analysis on fresh frozen tumor biopsies as a therapeutic decision tool for metastatic cancer patients, with solid cancers (SHIVA, MOSCATO) or specifically with breast cancer (SAFIR01, SAFIR02). All patients gave their informed consent for translational research and genetic analyses of their somatic DNA. Overall, whole-exome sequencing for a total of 216 pairs of metastatic tumor and unmutated DNA derived from corresponding blood samples was performed using Illumina technology. The results of the analysis of the mutational profile of metastatic breast cancer was reported in Lefebvre et al. (PMID:28027327).

  Study EGAS00001001695

• A sequence-based genetic dissection of human immune cell types and implications for immune-related disease.

  The immune system is an intricate biological network mediating interactions with other organisms while preserving the integrity of our tissues. By mounting appropriate responses it protects us from a vast range of pathogens while inadvertent immune system attacks on self result in autoimmune diseases. The project aims to discover whether and to what extent the behaviour of the immune system is genetically regulated and to detect the relationships of diverse immune cells with autoimmunity. The project consists of the genetic analysis using up to ~8.2 Million variants, deriving from high density genotyping data and low pass whole genome sequencing, and quantitative levels of 95 cell types encompassing 272 immune traits, in a cohort of 1,629 individuals from four clustered Sardinian villages belonging to the SardiNIA/ProgeNIA study.

  Study EGAS00001000574