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• Phase IB/II Study of Bazedoxifene in Combination with Palbociclib in Patients with Endocrine Resistant Hormone Receptor-Positive Breast Cancer

  In this phase Ib/II clinical trial, the investigators evaluated the efficacy and safety of the combination of palbociclib with bazedoxifene in patients with a metastatic endocrine-resistant hormone receptor-positive, HER2-negative breast cancer. Furthermore, whole exome sequencing of cell-free tumor DNA was done on serial samples from these patients, revealing potential molecular changes associated with mechanisms of resistance.

  Study phs002802

• NHLBI TOPMed - NHGRI CCDG: Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

  This study contains whole genome sequence data. A case-control sample of individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a multicenter prospective cohort study of 16,415 persons of Cuban, Dominican, Mexican, Puerto Rican, Central American, and South American background (phs000810), was selected for whole genome sequencing, including participants with a history of physician-diagnosed asthma and asthma-free participants.

  Study phs001395

• Molecular Correlatives from SU2C-SARC032

  SU2C-SARC032 was a phase II international, randomized trial for patients with localized, high-risk undifferentiated pleomorphic sarcoma or dedifferentiated or pleomorphic liposarcoma of the extremity and limb girdle. On the trial, the addition of perioperative pembrolizumab to preoperative radiotherapy and surgery improved disease-free survival compared to preoperative radiotherapy and surgery alone. Bulk RNA-sequencing was performed on pre-treatment and surgically resected tumor specimens.

  Study phs003921

• Study assessing the efficacy and safety of durvalumab plus olaparib plus fulvestrant in selected metastatic or locally advanced ER-positive, HER2-negative breast cancer patients.

  This study aims to evaluate the efficacy of the combination of olaparib, durvalumab, and fulvestrant for the treatment of patients with ER-positive, HER2-negative, locally advanced or metastatic breast cancer with BRCA gene alterations or alterations of genes involved in HRR or MSI status, in terms of the progression-free survival rate (PFSR) at 24 weeks.

  Study EGAS50000001166

• Sensitive circulating tumor DNA based residual disease detection in epithelial ovarian cancer

  In this study we implemented a circulating tumor DNA (ctDNA) based blood test for more accurate post-operative surveillance of this disease. We analyzed 264 plasma samples collected between June 2016 and September 2021 from 63 epithelial ovarian cancer patients using tumor-guided plasma cell-free DNA analysis to detect residual disease after treatment. Assay specificity was verified using cross-patient analysis of 1195 control samples.

  Study EGAS50000000245

• 46 patients primary malignant glioma cohort in Chinese population

  We recruited 46 Chinese patients with primary malignant glioma. All the patients were analyzed with whole-exome sequencing (WES) and 27 of them were analyzed with RNA-seq. We compared the molecular features between patients in different WHO grades. We used six-month progression-free survival (PFS6) status to group glioblastoma (GBM) patients to a good and a poor survival compared two groups genomic profiles.

  Study EGAS00001005583

• Transcriptomic subgroups in soft tissue tumors correlate with morphologic subtype, genomic features, and outcome

  We assessed gene expression (GGE) profiles and gene fusions as detected by transcriptome sequencing (RNA-seq) of 704 soft tissue tumors (STT) representing 56 different tumor types. Comparison with follow-up data identified transcriptional subclusters among sarcomas with complex genomes and among adipocytic tumors that correlated with metastasis-free survival and local recurrences, respectively. Thus, RNA-seq analysis of STT provides clinically important information.

  Study EGAS50000001472

• Genome-Wide Pleiotropy Scan Across Multiple Cancers

  A whole-exome sequencing (WES) study was conducted in 3,233 cases diagnosed with multiple primary cancers and 3,229 matched cancer-free controls (90% non-Hispanic white, 3% African-American, 3% East Asian, and 4% Latino) selected from individuals in the Kaiser Permanente Research Bank (KPRB) who were members of the Kaiser Permanente Northern California (KPNC) health plan. Cancer-free controls were matched to cases on age at specimen collection (within 2 years), sex, genotyping array (which matched on self-reported race/ethnicity), closest distance using the first two principal components for genetic ancestry, and reagent kit. Cases and controls were drawn from two prospective KPRB cohorts: the Research Program on Genes, Environment and Health (RPGEH) and the ProHealth study. Participants were sequenced by the Regeneron Genetics Center using the Illumina NovaSeq 6000 platform, and sample preparation and quality control were performed using a high-throughput, fully-automated system [PMID: 33087929]. Reads were aligned to the GRCh38 reference genome, and variants were called using WeCall [PMID: 33087929]. Participants with sex discordance, 20x coverage at less than 80% of targeted sites, and/or contamination greater than 5% were excluded. After quality control, we retained n = 6,247 (3,111 cases, 3,136 controls) individuals for downstream analyses. Among participants selected for this WES study, n = 5,432 (2,299 cases; 3,133 controls) consented to deposition of data to the National Institutes of Health (NIH).Further quality control was applied to filter low quality variants. Genotype calls with low depth of coverage (DP) were updated to missing (DP < 7 for SNPs and DP < 10 for indels), after which sites with low allele balance (AB) - variants without at least one sample having AB ≥ 15% for SNPs or AB ≥ 20% for indels - were removed. Lastly, variants with missingness > 10% and Hardy-Weinberg equilibrium p-value < 10-15 were excluded. Further description of quality control and downstream single-variant and gene-based analyses is available in Cavazos et al, 2022 [medRxiv].

  Study phs002809

• Luminal progenitor cell line iHBEC(CD117)

  Basal-like breast cancer originates in luminal progenitors, frequently with an altered PI3K pathway, and focally in close association with genetically altered myoepithelial cells at the site of tumor initiation. The exact trajectory behind this bi-lineage phenomenon remains poorly understood. Here we used a breast cancer relevant transduction protocol including hTERT, shp16, shp53, and PIK3CA(H1047R) to immortalize FACS isolated luminal cells, and we identified a candidate multipotent progenitor. We found that the apparent luminal phenotype of these oncogene transduced progenitors was metastable giving rise to basal-like cells dependent on culture conditions. After culturing the cells for more than 60 passages, cells were subjected to scRNA-seq as well as bulk RNA sequencing of two subpopulations (CD271+ and CD271-).

  Dataset EGAD50000000723

• DAC for Liquid CNA in High Grade Serous Ovarian Cancer

  Low pass sequencing of sequential cell free and tumour DNA with matched whole genome sequencing from five patients with high grade serous ovarian cancer presented in Hockings et al Cancer Research paper, 2025.

  Dac EGAC50000000648

• Long-read sequencing for cell-free DNA analysis (human pacbio)

  8 pregnant women at the 3rd trimesters, 4 hepatitis B carriers, and 4 patients with hepatocellular carcinoma

  Study EGAS00001006609

• NanoRCS and Reference samples

  Genome-wide NanoRCS of cell-free DNA from plasma of healthy controls (4 samples) Genome-wide sequencing of reference blood sample of healthy controls (4 samples)

  Dataset EGAD50000000974

• Long cell-free DNA molecules in maternal plasma (dataset1)

  Bam files consists PET cases and healthy cases

  Dataset EGAD00001008721

• sWGS of non-cancer controls

  Paired end shallow whole genome sequencing (sWGS) data of cell-free DNA from plasma from self-reporting healthy individuals (MonRec Cohort)

  Dataset EGAD00001005805

• Exploring the cell-free total RNA transcriptome in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma patients as biomarker source in blood plasma liquid biopsies

  The goal of this study was to investigate cell-free RNA (cfRNA) biomarkers in DLBCL and PMBCL patients. Blood plasma samples (n=168) and matched diagnostic formalin-fixed paraffin-embedded (FFPE) tissue samples (n=69) of DLBCL patients, PMBCL patients and healthy controls were collected between 2016-2021. Plasma samples were collected at diagnosis, at interim evaluation, after treatment, and in case of refractory or relapsed disease. RNA was extracted from 200 µl plasma using the miRNeasy serum/plasma kit and from FFPE tissue using the miRNeasy FFPE kit. RNA was subsequently sequenced on a NovaSeq 6000 instrument using the SMARTer Stranded Total RNA-seq pico v3 library preparation kit.

  Study EGAS00001007585

• Genomics Define Malignant Transformation in Myeloma Precursor Conditions

  Multiple myeloma (MM) is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). While these precursor conditions are asymptomatic, they are not entirely benign and carry a lifelong risk of progression to MM. Unlike other cancers defined by pathology, malignant transformation from MGUS or SMM to MM has so far relied on demonstration of clinical end-organ damage as morphology and cytogenetics cannot reliably distinguish them. In this study, using genomic data from 374 patients with MGUS or SMM (277 training, 97 validation), to our knowledge, we demonstrate for the first time the ability to identify malignant transformation in MGUS and SMM. We introduce the concept of genomic MM and genomic MGUS to differentiate the subsets of MGUS and SMM that are biologically malignant with genomic features indistinguishable from MM from the subset that is premalignant and unlikely to progress to malignancy. Importantly, we find that most SMM has biological features of malignant transformation indistinguishable from MM. As expected, this subset that we consider having genomic MM is associated with a high risk of progression to MM although some patients remained progression-free beyond 5 years. Conversely, 60% of MGUS and 10% of SMM have no evidence of malignant transformation (genomic MGUS), with no progression during follow-up. Integration of genomic features with the 2/20/20 International Myeloma Working Group model significantly improved the prediction of progression among genomic MM. These findings support the use of genomic criteria to refine the classification and the risk stratification in myeloma precursor conditions.

  Dataset EGAD00001015768

• Distribution of ctDNA levels in plasma of early-stage non-small cell lung cancer patients measured using personalised ctDNA analysis

  Blood-based assays have shown increasing ability to detect circulating tumour DNA (ctDNA) in patients with early-stage cancer. However, detection of ctDNA in patients with non-small cell lung cancer (NSCLC) has continued to prove challenging. We performed retrospective analysis to quantify ctDNA levels in a cohort of 100 patients with early-stage NSCLC prior to treatment with curative intent. Where tumour tissue was available for whole exome sequencing, mutations identified were used to define patient-specific sequencing assays. For those 90 patients, plasma cell-free DNA was sequenced to high depth across capture panels targeting a median of 328 mutations specific to each patient. Data was analysed using Integration of Variant Reads (INVAR), detecting ctDNA in 66.7% of patients, including 52.7% (29 of 55) patients with stage I disease and >88% detection for patients with stage II and III disease (16/18 and 15/17). ctDNA was detected in plasma at fractional concentrations as low as 9.1x10-6, and in patients with tumour volumes as low as 0.23 cm3. A 36-gene sequencing panel (InVisionFirst-LungTM) was used to analyse plasma DNA in 27 samples including the 10 cases without tumour exome data, and detected ctDNA in 59% of samples tested (16 of 27). Across the entire cohort, detection rates were higher in squamous cell carcinoma patients compared to adenocarcinoma patients (81% vs. 59%). Detection of ctDNA prior to treatment was associated with significantly shorter time free from relapse, across all patients and in patient subgroups, with Hazard Ratios ranging from 2.25 to >11. Our analysis indicates that for patients with stage I NSCLC, the median ctDNA fraction in plasma is approx. 12 parts per million (0.0012%). This indicates the limits of detection that would be required for ctDNA-based liquid biopsies to detect ctDNA in the majority of patients with early-stage NSCLC.

  Dataset EGAD00001006230

• Transcriptional Profiling of Macrophages In Situ in Metastatic Melanoma Reveals Localization-Dependent Phenotypes and Function

  Therapeutic interventions modulating immune function at the tumor site could improve outcomes in cancer. Here we analyzed metastatic melanoma, a tumor type highly responsive to T-cell based therapies, and found that the tumor-infiltrating T cells are localized closely to CD14+ monocytes/macrophages rather than to melanoma cells. Using novel immunofluorescence-guided laser capture micro-dissection, we analyzed transcriptomes of CD3+ T cells, CD14+ monocytes/macrophages and melanoma cells in non-dissociated tissue. CD14+ cells localized in tumors beds displayed specific transcriptional signatures distinct from CD14+ cells that were localized in tumor stroma.The 8 distinct metastatic melanoma samples are from the Cooperative Human Tissue Network (CHTN). 64 RNA-seq files are available from 16 intraCD14+, 16 stromaCD14+, 16 cancer cells, 8 intraCD3+ and 8 stromaCD3+ cells. 2 LCM harvests were completed for the CD14+ and cancer cells on two sections of the samples. One harvest was done for the CD3+ samples.The processed data (TPM/raw counts tables) are available on GEO under GSE180124. 

  Study phs002564

• Genomic Profiling of Sequentially Acquired Metastatic Sites from an "Exceptional Responder" Lung Adenocarcinoma Patient Reveals Extensive Genomic Heterogeneity and Novel Somatic Variants

  We employed next-generation sequencing to identify somatic alterations in multiple metastatic sites from an "exceptional responder" lung adenocarcinoma patient during his seven year course of ERBB2-directed therapies. The degree of heterogeneity was unprecedented, with ~1% similarity between somatic alterations of the lung and lymph nodes. One novel translocation, PLAG1-ACTA2, present in both sites, up-regulated ACTA2 expression. ERBB2, the predominant driver oncogene, was amplified in both sites, more pronounced in the lung, and harbored an L869R mutation in the lymph node. Functional studies demonstrated increased proliferation, migration, metastasis, and resistance to ERBB2-directed therapy due to L869R mutation and increased migration due to ACTA2 overexpression. Within the lung, a nonfunctional CDK12, due to a novel G879V mutation, correlated with down-regulation of DNA damage response genes, causing genomic instability, and sensitivity to chemotherapy. We propose a model whereby a sub-clone metastasized early from the primary site and evolved independently in lymph nodes.

  Study phs001159

• WES in HCCOs with varying Doxorubicin resistance

  We aimed to identify somatic mutations that could explain the resistance to Doxorubicin. Therefor, we purified Exomes from liver biopsies and HCC organoids using Agilent SureSelectXT (clinical research exome, HS2 V8, or Human all Exon V6 Cosmic) and performed WES. Matched non-tumoral liver biopsies served as the control for germline mutations. 12 of these samples were previously reported. Sequence reads were aligned to the reference human genome GRCh38 using Burrows-Wheeler Aligner (BWA, v0.7.17). Duplicate removal, base quality adjustment, mutation calling (Mutect2, intervals: SureSelectXT_HS_V8_S33266340, germline-recourse: gnomad.exomes.r2.1.1.sites.liftover_grch38, Panel-of-Normal: 1000g_pon.hg38), filtering of Mutect calls, and functional annotation (Funcotator, funcotator_dataSources.v1.7.20200521g) were performed using the Genome Analysis Toolkit (GATK, v4.4) according to the Broad Institute best practices in Somatic short variant discovery workflows. Mutations with a functional annotation of Deletion, Insertion, Non-stop, Splice-Site, Start-Codon and Missense mutations were kept. A list of 43 commonly mutated genes in HCC was analyzed in the HCC organoids [TCGA, Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma. Cell, 2017. 169(7): p. 1327-1341.e23].

  Study EGAS50000000043

• An Isogenic Cell Line Panel for Sequence-based Screening of Targeted Anti-cancer Drugs

  We describe the creation and characterization of an isogenic cell line panel representing common cancer pathways, with multiple features optimized for high-throughput screening. More than 1,800 cell lines from three normal human cells were generated using CRISPR-technologies. Surprisingly, we discovered most of these lines did not result in complete gene inactivation, despite integration of sgRNA at the desired genomic site. However, a subset of the lines harbored true, biallelic disruptions of the targeted tumor suppressor gene, yielding a final panel of 100 well-characterize lines covering 19 pathways frequently subject to loss of function in cancers. This panel included genetic markers optimized for sequence-based ratiometric assays for drug-based screening assays. To illustrate the potential utility of this panel, we developed a multiplexed high-throughput screen that identified Wee1 inhibitor MK-1775 as a selective growth inhibitor of cells with inactivation of TP53. These cell lines and screening approach should prove useful for researchers studying a variety of cellular and biochemical phenomena

  Study EGAS00001005974

• The British Autozygosity Populations BioResource (2022-04-26)

  This data set contains whole exome sequences of individuals from 8086 (mostly British Pakistani/British Bangladeshi, mostly self-reported parentally related) individuals from the following studies: 1. 5236 British Pakistani/British Bangladeshi adults from East London Genes & Health, now known as Genes & Health 2. 2624 British South Asian mothers from Born in Bradford (mostly Pakistani) 3. 1061 British South Asian adults from Birmingham (mostly Pakistani) This dataset contains all the exome sequence data available for this study on 2022-04-26

  Dataset EGAD00001008736

• sWGS of cfDNA from plasma and urine

  Shallow WGS data from cell-free DNA extracted from plasma and urine (stored under different storage conditions)

  Dataset EGAD50000001587

• Clinical data

  Clinical data from AVANT: Clinical data include race, age, sex, baseline ecog, tumor stage, node status, treatment arm, KRAS and BRAF mutation status, tumor location, concensus molecular subtype, overall survival and disease free survival for 797 patients across AVANT.

  Dataset EGAD00001009727

• Long-read sequencing for cell-free DNA analysis (human pacbio)

  8 pregnant women at the 3rd trimesters, 4 hepatitis B carriers, and 4 patients with hepatocellular carcinoma

  Dataset EGAD00001009427