4984 results for "*oma"

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• Reading about genomic analysis of pan-neuroblastoma

  There are virtually no research fields that do not benefit from the large-scale genomic analysis that are so popular nowadays. For research into diseases with highly diverse clinical behavior like pediatric neuroblastoma, nevertheless, this type of approach has been a game-changer. Samuel W. Brady and colleagues, from St. Jude Children’s Research Hospital in Memphis, have gathered data from 702 neuroblastomas which were profiled by whole genome sequencing (WGS, n = 205), whole exome sequencing (WES, n = 539), and/or RNA-Seq. Less than half of the samples were generated during this study, while the others were obtained from previous work. Part of the WES data was indeed deposited in EGA in 2012 (EGA study EGAS00001000213). A scratchy summary about the huge work from Samuel W. Brady and colleagues, published in Nature Communications this October 2020 “These findings suggest that the sympathetic nervous system, the tissue from which neuroblastoma arises, is susceptible to different oncogenic insults at different times during development, which could be explored in future investigations using animal models.” Conclude the authors, highlighting the importance of their findings. Pediatric neuroblastomas are classified according to clinical and molecular features into low, intermediate, and high risk. Age plays a critical role in the classification, with younger children having an overall better prognosis. The samples included in this study belonged to all ages and risk-groups: the aim of such set up is the identification of age-associated molecular aberrations. The authors defined a mutational landscape of pediatric neuroblastoma including rare driver events, impossible to pick with a smaller data set. Interestingly, most driver mutations' frequency was found to be age-related. Those include alterations on MYCN, TERT, PTPRD, and Ras pathway, in addition to the previously reported ATRX. In addition, the large data set allowed the authors to define co-existence relations between the mutations (mutual exclusion or co-occurrence) which is a crucial puzzle piece to unravel the mechanisms driving the pathogenesis. Enjoy this really interesting article, open source on Pubmed.

  Blog genomic-analysis-of-pan-neuroblastoma

• Drug development for pediatric cancers: the importance of patient' s genomic data re-use

  Cancer in children is uncommon and the overall prognosis for most pediatric cancers is good. However, while the combined survival rates have improved over the last decades, certain childhood malignancies, such as high-grade gliomas or metastatic sarcomas, still remain incurable in most patients. New strategies for targeting those devastating diseases are imperative, and patient genomic data can become a key asset in the process [1]. The Pediatric Cancer Genome Project’s datasets At EGA, we store over 500 datasets with sequencing data from pediatric cancer patients. A remarkable case is the datasets belonging to the Pediatric Cancer Genome Project (PCGP) from St. Jude Children’s Research Hospital–Washington University (Table 1 - EGAS list). PCGP is an ambitious effort to identify the mutations that drive childhood cancer and find new cures. Those datasets include 600 patients with complete tumor and normal genomes from 15 different tumor types. PCGP datasets have been an important resource for various studies that pooled genomic data from different public and in-house datasets to perform extensive genomic characterizations and publish comprehensive pan-cancer pediatric studies [2],[3]. Other interesting pediatric cancer datasets are from the Pediatric Brain Tumor Consortium, Sickkids or ICGC PedBrain project. How data reuse impacts drug development for pediatric cancers Recently, in October 2024, Nature Communications published a work led by the University of Michigan where authors used data from EGA (PCGP) check the table below as part of their strategy to pursue the identification of new tumor vulnerabilities susceptible to becoming novel therapeutic targets in diffuse midline glioma. Diffuse midline gliomas (DMG) are treatment-resistant and uniformly fatal pediatric brain tumors. The prognosis of this brainstem tumor is dismal with a median overall survival of 9–12 months from diagnosis. In this study, the authors first developed a lab model of the disease and reanalyzed data from the EGA to identify genes potentially linked to tumor severity. This approach revealed involvement of specific metabolic pathways, suggesting new possibilities for therapeutic intervention. In mice, the study shows that the use of statins can improve survival. For a brief overview of the underlying science, diffuse midline gliomas present intratumor heterogeneity with subpopulations of less-differentiated oligodendrocyte precursors and more differentiated astrocytes. Authors established in vitro models to recapitulate both phenotypes and identify metabolic programs in both subpopulations. To determine the clinical relevance, the authors re-used gene expression data from 76 DMG patients identifying a gene signature predicting decreased overall survival. After extensive metabolic characterization of subpopulations, authors defined strategies to target specific metabolic vulnerabilities. Pre-clinical experiments in mice using OXPHOS inhibitors and statins showed a reduction in tumor burden and increased overall survival [4]. In this scenario, the re-use of high-quality patient’s sequencing data appeared as an advantageous strategy to support the clinical relevance of in-vitro and pre-clinical findings. On the other hand, in rare conditions such as childhood cancer, the availability of public datasets and the possibility of pooling data from different sources can be the only way to obtain impactful results that lead to improvements for patients. References Davidoff, A. M. Pediatric Oncology. Seminars in pediatric surgery 19, 225–233 (2010). Gröbner, S. N. et al. The landscape of genomic alterations across childhood cancers. Nature 555, 321–327 (2018). Venu Thatikonda et al. Comprehensive analysis of mutational signatures reveals distinct patterns and molecular processes across 27 pediatric cancers. Nature Cancer 4, 276–289 (2023). Mbah, N. E. et al. Therapeutic targeting of differentiation-state dependent metabolic vulnerabilities in diffuse midline glioma. Nature Communications 15, (2024). Datasets and Studies ID Title Access Policy Year EGAD00001000134 Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma McGill-DKFZ Pediatric Brain Tumour Consortium 2016 EGAS0000100192 Somatic Histone H3 Mutations in Diffuse Intrinsic Pontine Gliomas and Non-Brainstem Paediatric Glioblastomas St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project 2017 EGAS00001000575 Whole genome sequencing and whole exome sequencing of DIPG tumors and matched normal tissue The hospital for sick children ("SickKids") 2016 EGAD00001000792 Exome sequencing reads of paediatric glioblastoma McGill-DKFZ Pediatric Brain Tumour Consortium 2016 EGAD00001002006 Whole genome sequencing of paediatric glioblastoma in the ICGC PedBrain project ICGC PedBrain project 2016

  Blog drug-development-for-pediatric-cancers

• Highlights from 2025: Our top 10 requested studies

  In 2025, as in previous years, EGA has facilitated the reuse of numerous datasets spanning a broad range of research and healthcare topics. To reflect on this activity, we would like to highlight the top 10 studies behind the most requested datasets of last year. Notably, the vast majority of these highly requested datasets are cancer-focused, particularly involving the study of immune checkpoint inhibitor therapies. Immune checkpoint inhibitors (ICIs) have become one of the most transformative advances in modern cancer therapy. These monoclonal antibodies enhance antitumor immune responses by targeting inhibitory immune checkpoint molecules. While ICIs have led to remarkably favorable and durable responses in some patients, treatment outcomes vary widely. This variability has fueled intense research efforts aimed at understanding resistance mechanisms, exploring combination therapies, and discovering predictive biomarkers to better stratify patients and guide treatment decisions. Study Title Disease 1 EGAS00001005503 Integrated genomic analyses reveal molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma Liver Cancer 2 EGAS00001005013 Intratumoral plasma cells predict outcomes to PD-L1 blockade in non-small cell lung cancer Lung Cancer 3 EGAS00001004809 BIOKEY: A single-cell catalogue of the dynamic changes underlying Checkpoint Immunotherapy response in Early Breast Cancer Breast Cancer 4 EGAS50000000138 BIOKEY: Immune heterogeneity in small cell lung cancer and vulnerability to immune checkpoint blockade Lung Cancer 5 EGAS50000000497 Bladder cancer subtyping study across 4 atezo clinical trials Bladder Cancer 6 EGAS50000000689 MOSAIC - Multi-Omics Spatial Atlas In Cancer Cancer Atlas 7 EGAS00000000083 METABRIC (Breast cancer - genome and transcriptome) Breast Cancer 8 EGAS00001005702 Human genomic and phenotypic synthetic data for the study of rare diseases Synthetic data 9 EGAS00001002556 TGF-β attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells Bladder Cancer 10 EGAS00001004353 Molecular subsets in renal cancer determine outcome to checkpoint and angiogenesis blockade Renal Cancer The most requested dataset of the year was EGAD00001008128. It belongs to a study that analyzed 358 liver cancer patients enrolled in clinical trials and treated with the combination of atezolizumab (anti–PD-L1) and bevacizumab (anti-VEGF), atezolizumab alone, or sorafenib. The study highlights how bevacizumab enhances anti-PD-L1 effect and identifies candidate biomarkers to predict treatment response. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the third leading cause of cancer-related death worldwide [1]. Because symptoms often appear late, many patients are diagnosed at advanced stages, when curative options are no longer viable. For many years, sorafenib—a multikinase inhibitor approved in 2007—was the only systemic treatment available. Although numerous clinical trials followed, it was not until a decade later that additional therapies showed meaningful clinical benefit. Among these advances, immunotherapy emerged as a promising first-line option [2]. In particular, the combination of atezolizumab and bevacizumab demonstrated improved survival in patients with advanced HCC, reshaping the treatment landscape. However, treatment efficacy remains limited by the complex and diverse hepatic microenvironments that influence immune responses, as well as by high intratumoral heterogeneity. Identifying robust predictors of treatment response is critical to enable effective patient stratification and maximize the benefits of these therapies [2]. The continued demand for these datasets highlights the interest and critical role of data reuse in deepening our understanding of cancer, accelerating the development of more effective therapies, and improving patient outcomes. By providing secure access to high-quality genomic and clinical data, EGA acts as a catalyst for biomedical progress. References Sung, Hyuna, et al. "Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries."CA: a cancer journal for clinicians 71.3 (2021): 209-249. Ladd, Alexandra D, et al.“Mechanisms of drug resistance in HCC.” Hepatology 79(4) (2024): 926-940

  Blog top-10-studies-2025

• Methylation Biomarkers can Distinguish Pleural Mesothelioma from Healthy Pleura and other Pleural Pathologies

  Pleural mesothelioma (PM) is a rare cancer type. This study developed a methylation-based biomarker assay to distinguish PM from healthy pleura and other pleural conditions. By analyzing methylation data, 744 hypermethylated CpG sites specific to PM were identified and validated with high accuracy. Using the bisulfite-free IMPRESS technique, the assay was further validated in a diverse cohort, showing strong performance in distinguishing tumoral from non-tumoral samples and PM from pleural metastases. These findings support the assay’s potential as a robust diagnostic tool for PM.

  Study EGAS00001008153

• Pineoblastoma Single-Nuclei RNA-seq Data Access Committee (St. Jude)

  Committee responsible for reviewing and approving external access requests to controlled-access pediatric brain tumor transcriptomic datasets from St. Jude Children's Research Hospital, ensuring alignment with patient consent and institutional ethics policies.

  Dac EGAC50000000839

• Androgen activity in the normal male embryonic hindbrain drives lethal PFA ependymoma

  PFA ependymoma is an unusual infantile brain tumor with few somatic mutations, thought to be driven by epigenetic mechanisms. PFA ependymomas have a markedly higher incidence, and a worse prognosis in males as compared to female infants. Here we show that the cellular hierarchy of male PFA is less differentiated than female PFA. Androgen supplementation promotes the growth of PFA ependymoma. We conclude that androgen signaling in both the normal developing hindbrain, and PFA ependymoma are both necessary and sufficient to promote growth and delay differentiation.

  Study EGAS50000000507

• Plasma cell‐free transcriptome profiling in chronic liver disease

  RNAseq data from plasma samples corresponding to a Grand Challenge Programme project to find biomarkers for liver disease, including NAFLD, NASH, Cirrhosis and Hepatocelullarcarcinoma. A template of the DTA and DAA files is available in the following zenodo repository https://doi.org/10.5281/zenodo.19047046.

  Dac EGAC50000000360

• DAC for "H3K27me3-mediated epigenetic repression regulates neuroblastoma development and contributes to biological heterogeneity"

  Dac EGAC00001003620

• Single-cell bisulfite-seq analyses of 1-year-old prospermatogonia and adult spermatogonial stem cell

  To examine the timing of de novo methylation during human male germ cell development, single-cell bisulfite sequencing was carried out on human germ cells. FACS-purified Prospermatogonia from three teratoma patients (1-year-0-month, 1-year-5-months, and 1-year-8-months) and spermatogonial stem cells from a 29-year-old obstructive azoospermia patient with normal spermatogenesis were analyzed. The three 1-year-old prospermatogonia exhibited average methylation levels of 41.4% (23.1-54.4%, 1-year-0-month), 53.1% (32.0-62.4%, 1-year-5-months), and 32.6% (10.2-54.7%, 1-year-8-months). In contrast, adult spermatogonia showed an average level of 75.7% (73.3-76.8%). Although teratoma may have influenced the developmental timing of prospermatogonia within the same testes, prospermatogonia across all 1-year-old samples remained in an intermediate phase of DNA methylation establishment.

  Study JGAS000887

• Analysis of Large Cell Neuroendocrine Carcinoma Expressing POU2F3 Using WGS

  Lung LCNEC (Large Cell Neuroendocrine Carcinoma) has a poor prognosis, and no effective treatment has yet been established. We have found that the tuft-cell marker POU2F3 is specifically expressed in some LCNEC cases. By performing Whole Genome Sequencing (WGS) on samples from 10 LCNEC patients, we aim to identify changes characteristic of LCNEC expressing POU2F3 and explore new classifications and treatment options for LCNEC.

  Study JGAS000784

• Whole genome sequencing, single-cell RNA sequencing, and ATAC sequencing of mesothelioma (patient, patient-derived xenograft and cell line)

  Malignant pleural mesothelioma is an aggressive pleural tumor with a poor prognosis, and elucidating its molecular mechanisms is essential for improving diagnosis and treatment. This study investigates key genes and pathways involved in tumor progression, with particular attention to the involvement of neutrophils in the tumor ecosystem of mesothelioma. We performed whole-genome sequencing and single-cell RNA sequencing (scRNA-seq) of one pleural mesothelioma tumor specimen, scRNA-seq of matched patient-derived xenograft tumors, scRNA-seq of mesothelioma-free pleural tissues from three patients, and assay for transposase-accessible chromatin using sequencing (ATAC-seq) of a patient-derived cell line.

  Study JGAS000859

• Single-cell bisulfite-seq analyses of 29-year-old prospermatogonia and adult spermatogonial stem cell

  To examine the timing of de novo methylation during human male germ cell development, single-cell bisulfite sequencing was carried out on human germ cells. FACS-purified Prospermatogonia from three teratoma patients (1-year-0-month, 1-year-5-months, and 1-year-8-months) and spermatogonial stem cells from a 29-year-old obstructive azoospermia patient with normal spermatogenesis were analyzed. The three 1-year-old prospermatogonia exhibited average methylation levels of 41.4% (23.1-54.4%, 1-year-0-month), 53.1% (32.0-62.4%, 1-year-5-months), and 32.6% (10.2-54.7%, 1-year-8-months). In contrast, adult spermatogonia showed an average level of 75.7% (73.3-76.8%). Although teratoma may have influenced the developmental timing of prospermatogonia within the same testes, prospermatogonia across all 1-year-old samples remained in an intermediate phase of DNA methylation establishment.

  Study JGAS000888

• Genomic subtypes and cellular phenotypes of high-grade endometrial carcinoma

  Based on the mechanism of carcinogenesis, endometrial cancer (EC) is classified into two major types, Type I and Type II. Type I EC is characterized by G1/G2 histology, accounting for about 80% of all uterine carcinomas. On the other hand, Type II EC, which often develops after menopause, is estrogen-independent and consists of serous and clear cell carcinomas. G3 EC is often classified as a Type II EC, but the pathogenesis is thought to be a mixture of estrogen-dependent and estrogen-independent carcinogenesis. We will conduct an integrative genomic analysis to clarify the pathogenesis of Type II EC and redefine its classification by combining genomic status with cell phenotypes reflected in gene expression profiles.

  Study JGAS000753

• Whole-exome sequencing of uterine carcinosarcoma in a young woman with HBOC (tumor-normal pair)

  This study deposits controlled-access human genomic data (tumor-normal whole-exome sequencing) from a patient with uterine carcinosarcoma and hereditary breast and ovarian cancer (HBOC) syndrome, to support reproducibility of reported genomic findings.

  Study JGAS000883

• Molecular Characterization of Large Cell Neuroendocrine Carcinoma of the Lung by Multilayered Omics Analysis

  Large cell neuroendocrine carcinoma (LCNEC) is a rare lung cancer type with a very poor prognosis. The underlying molecular features remain unclear. Here, we conducted a multi-omics analysis of 27 LCNEC cases along with 7 small cell lung carcinoma and aimed to propose new classification by extracting genomic and transcriptomic features in LCNEC, leading to the elucidation of the therapeutic approaches.

  Study JGAS000832

• Whole exome and ChIP sequencing of external auditory canal squamous cell carcinoma (EACSCC)

  We performed whole exome sequencing of the primary tumor tissues, peripheral blood mononuclear cells from an EACSCC patient as well as the cell line established from the primary tumor tissues. We performed ChIP sequencing of primary tumor tissues and noncancerous ear skin tissues from EACSCC patients as well.

  Study JGAS000645

• Single cell atlas of large B-cell lymphoma

  Large B-cell lymphomas (LBCL) are clinically and biologically heterogeneous lymphoid malignancies, shaped by complex tumor and microenvironments that play a critical role in disease progression. There has been no direct and comprehensive single-cell characterization of tumor microenvironment in LBCL that simultaneously captures lymphoid, myeloid, and stromal populations across a sufficiently large cohort to reveal reproducible and biologically meaningful patterns. Here, we performed single-nucleus multiome profiling, coupled with bulk DNA and RNA sequencing, on 232 tumor and control biopsies to comprehensively map cell subpopulations of LBCL. Through this integrative approach, we identified Lymphoma Microenvironment Archetype Profiles (LymphoMAPs)—distinct, reproducible patterns defined by the co-occurrence of functionally specialized cell subsets. We further characterized the cell-cell communication pathways that shape these transcriptional phenotypes within archetypes. Importantly, we discovered associations between specific LymphoMAPs and clinical and molecular features of LBCL, including response to CD19 CAR T-cell therapy. Our study provides a valuable resource of lymphoid, myeloid, and non-hematopoietic cell states in LBCL and offers a framework for understanding how the abundance and functional state of cells within the tumor microenvironment may drive inter-patient variability in therapeutic outcome.

  Study EGAS50000001022

• Evolution of an adenomacarcinoma in response to selection by targeted kinase inhibitors

  Background - Adenocarcinomas of the tongue are rare and represent the minority (20-25%) of salivary gland tumors affecting the tongue. We investigated the utility of massively parallel sequencing to characterize an adenocarcinoma of the tongue, before and after treatment. Results - In the pre-treatment tumor we identified 7,629 genes within regions of copy number gain. 1,078 genes exhibited increased expression relative to the blood and unrelated tumors and four genes contained somatic protein-coding mutations. Our analysis suggested the tumor cells were driven by the RET oncogene. Genes whose protein products are targeted by the RET inhibitors sunitinib and sorafenib correlated with being amplified and or highly expressed. Consistent with our observations administration of sunitinib was associated with stable disease lasting 4 months, after which the lung lesions began to grow. Administration of sorafenib and sulindac provided disease stabilization for an additional 3 months after which the cancer progressed and new lesions appeared. A recurring metastasis possessed 7,288 genes within copy number amplicons, 385 genes exhibiting increased expression relative to other tumours and 9 new somatic protein coding mutations. The observed mutations and amplif ications were consistent with therapeutic resistance arising through activation of the MAPK and AKT pathways. Conclusions - We conclude that complete genomic characterization of a rare tumour has the potential to aid in clinical decision making and identifying therapeutic approaches where no established treatment protocols exist. These results also provide direct in-vivo genomic evidence for mutational evolution within a tumor under drug selection and potential mechanisms of drug resistance accrual.

  Study EGAS00000000074

• ARID1A Mutations in Endometriosis-Associated Ovarian Carcinomas

  We have sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas

  Study EGAS00000000075

• Multiple Myeloma treated with BCL2 inhibitor based treatment

  Whole Genome Sequencing from patients with multiple myeloma treated with BCL2 inhibitor based treatment.

  Study EGAS50000001479

• Familial Melanoma Sequencing

  In this experiment we have sequenced the exome of 15 individuals from eight families who have familial melanoma. By sequencing the exome we hope to be able to identify new genes that are associated with this disease.

  Study EGAS00001000017

• Osteosarcoma_Sequencing

  Genomic libraries (500 bps) will be generated from total genomic DNA derived from 25 osetocarcinoma samples and subjected to total of three lanes of 37 bp paired end sequencing on the llumina GA per sample. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.

  Study EGAS00001000013

• Transcriptomic profiling of circulating regulatory T cells from follicular lymphoma patients before and after Lenalidomide treatment

  Lenalidomide has demonstrated a favorable efficacy profile in follicular lymphoma (FL) in combination with anti-CD20 antibodies. However, in vivo administration of Lenalidomide in FL patients triggers a proliferation of functional regulatory T cells (Tregs), and a high percentage of Tregs before and along the course of treatment with Lenalidomide/anti-CD20 combination is of poor prognosis. In this study, we evaluated the impact of Lenalidomide on circulating Treg in 3 FL patients using single cell RNA sequencing (scRNAseq). For this purpose, we took advantage of the GALEN clinical trial (NCT01582776), where Lenalidomide was initiated one week before starting the anti-CD20 antibody Obinutuzumab, allowing us to compare the transcriptomic profile of immune cells before (D0) and at day 7 (D7) of treatment by Lenalidomide alone.

  Study EGAS50000001048

• Error-corrected flow-based sequencing at whole genome scale and its application to circulating cell-free DNA profiling

  Differentiating sequencing errors from true variants is a central genomics challenge calling for error suppression strategies that balance costs when sparse material or ultra-rare variants require high-accuracy methods. For example, circulating cell-free DNA (ccfDNA) sequencing for cancer monitoring is limited by sparsity of circulating tumor DNA (ctDNA), abundance of genomic material in samples, library preparation error rates and sequencing errors. Whole-genome sequencing (WGS) can overcome the low abundance of ccfDNA by integrating signal across the mutation landscape, but higher cost limits adoption compared with targeted panels, where ccfDNA abundance limits maximal coverage depths. Here we applied deep (~120x) lower-cost WGS (Ultima Genomics) with analytic error correction for tumor-informed ctDNA detection within the part-per-million range. We further developed high-coverage duplex error-corrected WGS of ccfDNA, achieving 7.7x10-8 error rates, to assess disease burden in melanoma and urothelial cancer patients without matched tumor sequencing. Together, we show that deeply sequenced error-corrected WGS accurately calls somatic variants, demonstrating the feasibility of WGS for tumor-informed and tumor-agnostic ctDNA detection.

  Study EGAS50000000844

• Genomic and transcriptome analysis for intrahepatic cholangiocarcinoma

  Study EGAS00001006007