5522 results for "*oma"

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• Predictive value of genomic, transcriptomic and epigenetic biomarkers in patients with recurrent and/or metastatic HNSC treated with PD-1/PD-L1 inhibitors

  Immune checkpoint inhibitors have improved survival in several solid tumors, including head and neck squamous cell carcinoma (HNSCC). However, current use of PD-1/PD-L1 inhibitors relies on PD-L1 expression, which does not reliably predict patient response. Therefore, better predictive biomarkers are needed to identify which patients benefit from immunotherapy. Previous studies suggest that genomic and transcriptomic features may help predict treatment response. This study aims to integrate genomic, transcriptomic, and methylomic data from 31 patients with recurrent/metastatic HNSCC to identify new biomarkers of resistance to anti-PD-1/PD-L1 therapy.

  Study EGAS50000001746

• A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies

  Pineoblastoma is a clinically aggressive childhood brain tumor composed of distinct molecular subgroups with divergent driver genes, demographics, and clinical outcomes. To identify developmental origins and mechanisms governing disease pathogenesis, we derive single-cell transcriptomes from pineal parenchymal tumors, aligning malignant cells with our atlas of pineal gland development to retrace cellular origins. Integrative computational analyses maps pineoblastoma origins to transient cycling pinealocyte progenitors during development. Lineage-specific perturbation of suspected drivers in the early pineal gland yields preclinical models representative of consensus molecular subgroups. Multi-omic characterization of patient tumors and these models uncovers a tumor-associated photoreceptor signature common to pineoblastoma, retinoblastoma, and Group 3 medulloblastoma. Transcriptional activity of this signature within respective cellular origins establishes a developmental basis for molecular similarities between entities. Photoreceptor signature constituents are selective dependencies across these anatomically distinct central nervous system malignancies, motivating future studies evaluating developmentally encoded programs of malignancy as potential therapeutic liabilities.

  Study EGAS50000001457

• ecDNA copy number heterogeneity

  Neuroblastoma exhibits significant inter- and intra-tumour genetic heterogeneity and varying clinical outcomes. Here, we used DNA and RNA sequencing from the same single cells in cell lines and neuroblastoma patients to investigate these effects. We reveal extensive intercellular ecDNA copy number heterogeneity. We also provide direct evidence of how this heterogeneity influences the expression of cargo genes, including MYCN and its downstream targets, and the overall transcriptional state of neuroblastoma cells.

  Study EGAS50000000509

• Single cell RNA sequencing of relapsed/refractory multiple myeloma

  Study EGAS00001004805

• Whole-exome sequencing of HPV-negative HNSCC to identify pathway alterations

  This study applies whole-exome sequencing (WES) to characterize genomic alterations in HPV-negative head and neck squamous cell carcinoma. Tumors were analyzed to derive pathway-level alteration scores, enabling stratification into Hedgehog-high and Hedgehog-low groups. The genomic data were integrated with imaging, transcriptomic, and functional analyses to investigate tumor-intrinsic Hedgehog signaling. The study aims to identify molecular features associated with biologically distinct tumor subgroups.

  Study EGAS50000001550

• Multi-omics datasets (WES, RNA-seq) of mesothelioma MIST2 study, a phase II CDK4/6 (abemaciclib) clinical trial

  This study comprises 26 mesothelioma patients with whole exome and RNA sequencing, to to assess potential sensitivity to CDK4/6 inhibition in p16ink4A-negative mesothelioma.

  Study EGAS50000001823

• Multi-omics datasets (WES, RNA-seq) of mesothelioma NERO study, a phase II PARP inhibitor clinical trial

  Niraparib Efficacy in Patient With Unresectable Mesothelioma, NERO, this randomised phase II trial is designed to evaluating the efficacy of the PARP inhibitor Niraparib versus active symptom control.

  Study EGAS50000001825

• RNA sequencing dataset of of explants treated with PRX3 inhibitor thiostrepton in mesothelioma

  This dataset includes 66 RNA sequences datasets of mesothelioma explants under three conditions: baseline, untreated control and thiostrepton treatment.

  Dataset EGAD50000002650

• Transcriptome profiling of HNSCC treated with PD1/PDL1

  Immune checkpoint inhibitors have improved survival in several solid tumors, including head and neck squamous cell carcinoma (HNSCC). However, current use of PD-1/PD-L1 inhibitors relies on PD-L1 expression, which does not reliably predict patient response. Therefore, better predictive biomarkers are needed to identify which patients benefit from immunotherapy. Previous studies suggest that genomic and transcriptomic features may help predict treatment response. This study aims to integrate genomic, transcriptomic, and methylomic data from 31 patients with recurrent/metastatic HNSCC to identify new biomarkers of resistance to anti-PD-1/PD-L1 therapy.

  Dataset EGAD50000002506

• Transcriptomic profiling of Hedgehog-high and Hedgehog-low HPV-negative HNSCC

  This study investigates transcriptomic differences between Hedgehog-high and Hedgehog-low HPV-negative head and neck squamous cell carcinoma (HNSCC). Tumors were stratified based on pathway-level genomic alteration scores and imaging-associated Hedgehog activity. RNA sequencing was performed on archival FFPE tumor samples to assess pathway activation and transcriptional programs associated with Hedgehog signaling. The dataset supports integrative radiogenomic and functional analyses of tumor-intrinsic signaling pathways.

  Study EGAS50000001549

• Anaplastic Large Cell Lymphoma Tumor Gene Expression Profiling

  Anaplastic large cell lymphoma tumor RNA-Seq

  Study EGAS50000001011

• Anaplastic Large Cell Lymphoma Gene Expression

  Anaplastic Large Cell Lymphoma Gene Expression Study

  Dataset EGAD50000001478

• Mayo Anaplastic Large Cell Lymphoma Gene Expression

  Dac EGAC50000000633

• scRNAseq data of primary and metastatic melanoma samples

  Paired-end 10x single-cell RNA sequencing data from 13 melanoma samples. Sequencing was performed on the Illumina NovaSeq 6000 using 10xGenomics Chromium Next GEM Single-Cell 5 Reagent Kits v2.

  Dataset EGAD50000000665

• Comprehensive Genomic Profiling of a National Cohort of Pediatric Papillary Thyroid Carcinoma in Hungary

  Pediatric papillary thyroid carcinoma (PTC) is a rare childhood malignancy with increasing incidence and distinct clinicopathological features, including high rate of locoregional metastases and different molecular background compared to adult cases. Traditional treatments (surgery, radioactive iodine) are effective but pose long-term risks, prompting the exploration of targeted therapies. We performed comprehensive genomic profiling on 21 pediatric PTC patients utilising the Illumina TruSight Oncology 500 platform and detected mutations, gene fusions, copy number variations and revealed tumor mutational burden.

  Study EGAS50000001833

• Comprehensive Genomic Profiling of a National Cohort of Pediatric Papillary Thyroid Carcinoma in Hungary

  Pediatric papillary thyroid carcinoma (PTC) is a rare childhood malignancy with increasing incidence and distinct clinicopathological features, including high rate of locoregional metastases and different molecular background compared to adult cases. Traditional treatments (surgery, radioactive iodine) are effective but pose long-term risks, prompting the exploration of targeted therapies. We performed comprehensive genomic profiling on 21 pediatric PTC patients applying Illumina TruSight Oncology 500 platform and detected mutations, gene fusions, copy number variations and revealed tumor mutational burden.

  Dataset EGAD50000002659

• WGS - germline - oral squamous cell carcinoma

  We conducted a retrospective, single-center Canadian cohort study of patients who underwent primary surgery for OSCC between 2010 and 2024. Nucleic acid quality was assessed using the 4150 TapeStation System (Agilent) prior to library preparation. WGS was performed on germline DNA, following Genome Analysis Toolkit’s (GATK) Best Practices and procedures, with a target of 30X deduplicated coverage per sample, using an Illumina NovaSeq 6000 instrument.

  Dataset EGAD50000002608

• WES and RNA sequencing of mesothelioma patients from CONFIRM clinical trial

  CONFIRM is a placebo controlled, double-blind randomised phase III clinical trial designed to investigate the efficacy of the anti-PD1 inhibitor nivolumab in patients with relapsed mesothelioma. This study applied the whole exome sequencing and transcriptomic sequencing to uncover determinants of efficacy in patients exhibiting the most extreme response outcomes.

  Study EGAS50000001814

• Multi-omics datasets (WES, RNA-seq) of mesothelioma MIST4 study, a phase II PD-L1/VEGF blockage clinical trial

  This study comprises 26 mesothelioma patients with whole exome and RNA sequencing, designed to examine the efficacy and correlates of response to dual inhibition of programmed death-ligand 1 and vascular endothelial growth factor inhibition.

  Study EGAS50000001818

• WES dataset of mesothelioma MIST4 study

  This dataset includes bam files from WES of 20 tumor samples and 18 matched normal samples.

  Dataset EGAD50000002633

• RNA sequencing dataset of mesothelioma MIST4 study

  This dataset includes BAM files from RNA-seq of 20 tumor samples.

  Dataset EGAD50000002634

• Multiple Myeloma treated with anti-BCMA T-cell-redirecting therapy (1st Batch)

  Bone marrow samples were collected from patients treated with either anti-BCMA CART and/or anti-BCMA TCE. All samples were sorted using the StemCell EasySep Human CD138 positive selection kit II (StemCell, Cambridge, MA). The positive CD138+ were submitted for WGS, using peripheral blood mononuclear cells as normal matched. WGS was carried out by the Molecular Genomics Core Facility at Moffitt Cancer Center contingent on the availability of high-quality pre-treatment samples. Germline DNA was obtained from peripheral blood mononuclear cells, while tumor DNA was extracted from CD138-enriched bone marrow aspirate specimens using magnetic bead-based selection. Genomic DNA was isolated using the AllPrep DNA/RNA/miRNA Universal Kit (Qiagen). For library preparation, 100 ng of genomic DNA was fragmented using the Covaris ML230 focused ultrasonicator (Covaris, Inc.), followed by library construction with the TruSeq DNA Nano Library Prep Kit (Illumina) in accordance with manufacturer instructions. Library quality and fragment size distribution were assessed via Agilent TapeStation, and quantification was performed using the Kapa Library Quantification Kit (Roche). Sequencing was conducted on the Illumina NovaSeq 6000 system using S4-300 reagent kits with a 2×150 bp paired-end configuration. Tumor samples were sequenced to a median coverage of 60×, and matched germline controls to 30×. Reference Genome: GRCh38.

  Dataset EGAD50000002632

• SV-based ctDNA detection in soft tissue sarcoma

  33 patients with localized soft tissue sarcoma consented for ctDNA tracking in the peri-operative and surveillance periods. WGS at a target of 15x coverage was performed from DNA extracted from FFPE of localized soft tissue sarcoma. Structural variants were identified from WGS and ddPCR assays were designed for tumor informed tracking of SV for ctDNA.

  Study EGAS50000001811

• SV Based ctDNA detection in localized soft tissue sarcoma

  WGS from FFPE for "Detecting ctDNA Using Personalized Structural Variants to Forecast Recurrence in Localized Soft Tissue Sarcoma." study. 33 patients had whole genome sequencing through the Illumina platform at an average depth of 15x. Tumor informed structural variants were identified and ddPCR assays were designed for individualized structural variant-based ctDNA detection.

  Dataset EGAD50000002614

• Multi-omics profiling identifies two epithelioid sarcoma molecular subtypes with distinct signaling and immune characteristics

  Epithelioid sarcoma (EpS) is an aggressive sarcoma, characterized by the loss of SMARCB1 expression. EpS is traditionally classified as distal or proximal according to clinicopathological features, but its molecular characteristics remain largely unknown. To establish an EpS molecular classification and uncover determinants of inter- and intra-patient heterogeneity in EpS, we used multi-omics profiling and integrated the genomic, transcriptional and methylome landscapes with single-cell RNA sequencing on fresh samples as well as spatial transcriptomics. We identified two molecular subtypes of EpS: “distal-like” and “proximal-like”, which were distinct from the histological subtypes. Distal-like tumors include all morphological distal subtypes and a subset of proximal and hybrid EpS. They express a specific molecular single-cell derived epithelial-to-mesenchymal transition signature, which associates with improved patient survival and includes Desmoglein 2 (DSG2), which we identify as a potential routine immunohistochemical biomarker to improve diagnosis. Distal-like EpS also display increased peri-tumoral CD8+ T cell infiltrates and specific tumor-immune cell interactions. Conversely, proximal-like EpS harbor a higher inter-tumoral molecular heterogeneity with some cases resembling other SMARCB1-deficient tumors by DNA methylation profiling, and increased intra-tumoral pro-tumoral macrophage infiltrates. Our study introduces a novel molecular classification of EpS with prognostic value, associated diagnostic biomarkers and distinct tumor immune microenvironments, which extends beyond traditional clinicopathological classification. This paves the way for precision medicine-based therapeutic strategies for patients with EpS.

  Dac EGAC50000000552

• Multiregional whole exome sequencing of mesothelioma tumors of MEDUSA cohort

  MEDUSA (Mesotheliomaevolution: deciphering druggable somatic alterations) is a translational research platform to build predictive models to stratify existing therapies. This study utilizes multiregional mesothelioma exome sequencing to infer a human evolutionary model of MPM tumorigenesis and understand the inter-relationships that exist between genomic ITH, host immune surveillance and clinical phenotype.

  Study EGAS50000001865

• MD Anderson Cancer Center HGSOC LRS Data Access Comittee

  Oxford Nanopore long-read sequencing was performed on six paired tumor-normal samples from patients with high-grade serous ovarian carcinoma. Reads were mapped to the GRCh38 reference genome, incorporating base modification information.

  Dac EGAC50000000597

• MEC/SEF rhabdomyosarcoma mRNA sequencing

  This project was undertaken to sequence and analyze mRNA expression in these tumor subtypes. We intended to discover distinctive patterns of tumor subtype gene expression in these subtypes. In addition, we used this data to discover expression differences between ESWR fusion positive and fusion negative MEC tumors.

  Study EGAS50000000535

• ASPSCR1-TFE3 gene fusion panel deep amplicon sequencing data

  Dataset contains compressed, paired-end Fastq files of deep amplicon sequencing data from a custom ASPSCR1-TFE3 gene fusion panel for three alveolar soft part sarcoma cases described in "Development and first-in-human CAR T therapy targeting the pathognomonic MiT-fusion driven protein GPNMB".

  Dataset EGAD50000002438

• A conserved enhancer in ecDNA-containing Medulloblastoma

  Extrachromosomal DNA (ecDNA) fundamentally reshapes the regulatory landscape of cancer cells by providing a platform for massive oncogene amplification and heightened chromatin accessibility. This research investigates how ecDNA-resident enhancers operate within large-scale molecular hubs to drive potent, long-range transcriptional activation that transcends standard chromosomal boundaries. By analyzing the unique structural configurations of these elements, the work identifies key mechanisms that contribute to rapid tumor evolution and significant phenotypic plasticity. These findings highlight the critical role of non-chromosomal regulatory elements in maintaining oncogenic signaling and suggest new avenues for therapeutic intervention in aggressive, ecDNA-driven malignancies.

  Study EGAS50000001609

• A conserved enhancer in ecDNA-containing Medulloblastoma

  Extrachromosomal DNA (ecDNA) fundamentally reshapes the regulatory landscape of cancer cells by providing a platform for massive oncogene amplification and heightened chromatin accessibility. This research investigates how ecDNA-resident enhancers operate within large-scale molecular hubs to drive potent, long-range transcriptional activation that transcends standard chromosomal boundaries. By analyzing the unique structural configurations of these elements, the work identifies key mechanisms that contribute to rapid tumor evolution and significant phenotypic plasticity. These findings highlight the critical role of non-chromosomal regulatory elements in maintaining oncogenic signaling and suggest new avenues for therapeutic intervention in aggressive, ecDNA-driven malignancies.

  Study EGAS50000001610

• A conserved enhancer in ecDNA-containing Medulloblastoma

  Extrachromosomal DNA (ecDNA) fundamentally reshapes the regulatory landscape of cancer cells by providing a platform for massive oncogene amplification and heightened chromatin accessibility. This research investigates how ecDNA-resident enhancers operate within large-scale molecular hubs to drive potent, long-range transcriptional activation that transcends standard chromosomal boundaries. By analyzing the unique structural configurations of these elements, the work identifies key mechanisms that contribute to rapid tumor evolution and significant phenotypic plasticity. These findings highlight the critical role of non-chromosomal regulatory elements in maintaining oncogenic signaling and suggest new avenues for therapeutic intervention in aggressive, ecDNA-driven malignancies.

  Study EGAS50000001608

• Whole exome RNA sequencing of FFPE material from 49 pediatric BCP-LBL patients.

  This study contain the results of whole exome-targeted transcriptome analyses of FFPE material from 49 pediatric B-cell precursor lymphoblastic lymphoma patients. Data are provided as Fastq files.

  Study EGAS50000000289

• Single-cell multi-omic profiling of glioblastoma-associated myeloid cells

  Study EGAS00001004871

• Immune activation in the tumor microenvironment of renal cell carcinoma

  Study describes immunological responses to immunotherapy (anti-PD-1, pembrolizumab) and targeted therapy (VEGFR inhibition, axitinib) as well as anti-CD3/CD28/CD2 (Immunocult) in a patient-derived ex vivo tumor model of renal cell carcinoma. Patient-derived ex vivo tumor models were established and their treatment response studied using material from eight renal cell carcinoma patients. Samples were collected under informed consent in HUS Helsinki University Hospital, Finland. The study aims to understand immunological treatment responses in the patient tumor microenvironment.

  Study EGAS50000001349

• Hepatoblastoma tumoroid biobank as a key resource for tumour genetics

  Study EGAS00001008251

• Non-Hodgkin Lymphoma WES Data Access Committee

  DAC for controlled access to whole exome sequencing (WES) data from NHL patients at University of Tabuk

  Dac EGAC50000000998

• Whole Exome Sequencing of Non-Hodgkin Lymphoma Patients in Tabuk, Saudi Arabia

  This study presents whole exome sequencing (WES) data from 20 Non-Hodgkin Lymphoma (NHL) patients. Samples represent diverse histopathological subtypes including Diffuse Large B-Cell Lymphoma (DLBCL), Follicular Lymphoma, and other NHL variants. Both nodal and extranodal disease origins are represented. Sequencing was performed to investigate the genomic landscape of NHL in a Saudi Arabian patient cohort.

  Study EGAS50000001776

• Whole Exome Sequencing of Non-Hodgkin Lymphoma Patients

  This dataset contains whole exome sequencing data from 20 Non-Hodgkin Lymphoma patients sequenced on the Illumina NovaSeq 6000 platform. Data includes paired-end FASTQ files (2×150 bp) for all samples representing diverse histopathological subtypes including DLBCL, Follicular Lymphoma, and other NHL variants from a Saudi Arabian cohort.

  Dataset EGAD50000002551

• SPEN loss drives extra-follicular diffuse large B cell lymphoma with female-specific lethality and TLR pathway therapeutic vulnerabilities

  Multiome (ATAC and GEX) sequencing for one rLN sample and one DLBCL sample

  Study EGAS50000001594

• Epigenetic characterization of glioblastoma stem cells

  Chromatin accessibility discriminates stem from mature cell populations, enabling the identification of primitive stem-like cells in primary tumors, such as glioblastoma (GBM) where self-renewing cells driving cancer progression and recurrence are prime targets for therapeutic intervention. We show, using single-cell chromatin accessibility, that primary human GBMs harbor a heterogeneous self-renewing population whose diversity is captured in patient-derived glioblastoma stem cells (GSCs). In-depth characterization of chromatin accessibility in GSCs identifies three GSC states: Reactive, Constructive, and Invasive, each governed by uniquely essential transcription factors and present within GBMs in varying proportions. Orthotopic xenografts reveal that GSC states associate with survival, and identify an invasive GSC signature predictive of low patient survival, in line with the higher invasive properties of Invasive state GSCs compared to Reactive and Constructive GSCs as shown by in vitro and in vivo assays. Our chromatin-driven characterization of GSC states improves prognostic precision and identifies dependencies to guide combination therapies.

  Study EGAS50000001804

• Chromatin profiling using Cut&Run technique of hepatoblastoma organoids

  CUT&RUN LoV-U profiling of b-catenin, LEF1 and TCF7L2 binding in biological replicates (Replicate A, Replicate B) of hepatoblastoma organoids: 10F, 13F, 13E, 17E, 22E and 135F.

  Dataset EGAD50000001749

• Single-cell RNA/ATAC multiome profiling of hepatoblastoma resection samples

  10x Genomics Chromium Next GEM Single Cell Multiome ATAC + Gene Expression data of hepatoblastoma tissue samples. BAM files containing sequencing data of resection material of PT13 and PT17.

  Dataset EGAD50000001750

• Circulating Cell-free DNA Whole Genome Sequencing from Head and Neck Cancer Patients

  This dataset contains plasma-derived circulating cell-free DNA (cfDNA) whole genome sequencing (WGS) data from patients diagnosed with head and neck squamous cell carcinoma. cfDNA was extracted from plasma collected at defined clinical timepoints.

  Dataset EGAD50000001828

• Epigenetic characterization of patient-derived glioblastoma stem cell (GSC)

  ATAC-Seq data on 43 samples of glioblastoma stem cells mapped to hg19. Fastq files are available. PMID: 33427645

  Dataset EGAD50000002603

• Rituximab-treated lymphoma patients show correlated deficiency in serological and T cell Spike-specific response after SARS-CoV-2 vaccination: insights from the CORSA Study.

  This study is part of the CORSA trial (NCT04345315), a prospective multicentric research project conducted by the Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” to investigate the immunologic response to mRNA SARS-CoV-2 vaccines in patients with hematologic malignancies (HM) and healthy individuals as controls (HC). The data in this repository refer to two subcohorts: 7 healthy controls and 10 lymphoma patients, randomly selected. Whole blood samples were collected to characterize T cell receptor (TCR) repertoire specificity against SARS-CoV-2 proteins before and after two BNT162b2 vaccination cycles, at baseline (before vaccination), 50 days after the first dose (V1), and 6 months after the first dose (V3). All participants were vaccinated under the Italian national campaign and provided informed consent following the Declaration of Helsinki. We investigated SARS-CoV-2-specific T cell responses through TCR repertoire profiling and examined correlations between serological and cellular responses in both patient and control groups. Using Next-Generation Sequencing (NGS) to characterize the CDR3 sequences of TCR β-chains from peripheral blood, we assessed clonal expansion (depth) and diversification (breadth) of SARS-CoV-2-specific T cell clonotypes over time, aiming to understand how cancer and its treatment influence vaccine-induced immunity in immunocompromised individuals.

  Study EGAS50000001205

• Malignant mesothelioma EWAS on European prospective study

  Study EGAS00001006432

• Cell-free DNA methylation profiling for non-invasive detection and classification of lymphoma

  Compared with traditional tissue biopsies used for lymphoma diagnosis, cell-free DNA methylation profiling offers a minimally invasive approach capable of capturing lymphoma-specific epigenetic alterations. This study investigates genome-wide methylation patterns in plasma using cell-free methylated DNA immunoprecipitation and sequencing (cfMeDIP-seq). Differential methylation analysis of discovery samples identified lymphoma-associated hypermethylated regions that were used to develop classification models for lymphoma detection. Validation analyses demonstrated high accuracy and strong associations between cfDNA methylation scores and independent measures of tumor burden and clinical outcome. These findings support cfDNA methylation profiling as a sensitive approach for non-invasive lymphoma diagnosis.

  Study EGAS50000001463

• Cell-free MeDIP-seq of plasma samples from lymphoma patients and healthy controls

  This dataset contains cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq) data generated from plasma samples of lymphoma patients and healthy controls. The study aims to characterize genome-wide methylation patterns of circulating cell-free DNA and identify hypermethylated regions associated with lymphoma. Sequencing libraries were prepared using cfMeDIP with anti-5-methylcytidine antibody enrichment and sequenced on an Illumina platform. The dataset supports differential methylation analyses and the development of classification models for lymphoma detection.

  Dataset EGAD50000002108

• Intratumoral Ploidy Dynamics in HCC

  Hepatocellular carcinoma (HCC) ranks as the fourth leading cause of cancer-related deaths. Effective therapies are limited, highlighting the critical need for stratification biomarkers to improve prognosis and predict treatment response. Polyploidization or hyperploidization, an early event observed in many solid cancers, may offer such potential. Here, we developed a new high throughput in situ quantitative approach to assess HCC ploidy profiles. This novel method highlights the presence of both Diploid (DP-) and Hyperploid (HP-) HCCs. RNA-seq profiling classified hyperploid HCCs as belonging to the proliferation subclass, predicting unfavourable clinical outcomes, and revealing a gene expression signature indicative of stemness. Spatially reconstructing nuclear ploidy also revealed DP/HP-HCCs with hyperploid nuclei forming discrete clusters within a predominantly diploid background. Remarkably, these emerging hyperploid foci shared a portion of their transcriptomic programme with fully developed hyperploid HCCs and displayed a signature of genomic instability, including upregulation of multiple DNA repair pathways in response to replication-associated DNA damage. Importantly, spatial transcriptomics of DP/HP HCC demonstrated that hyperploid tumor hepatocytes arise through whole-genome doubling of diploid tumor hepatocytes. Collectively, our findings underscore the prognostic value of nuclear ploidy profiling in HCC and suggest that hyperploid HCCs evolve clonally from intratumor hyperploid foci during tumor progression.

  Study EGAS00001008084