Search Results - EGA European Genome-Phenome Archive

scRNA-seq of Multiple Myeloma and Tumor Microenvironment Cells from Bone Marrow During CAR T-Cell Therapy

Multiple myeloma (MM) is a treatable, yet incurable, plasma cell malignancy for which molecular mechanisms driving the development of therapy resistance remain largely elusive. To better characterize tumor intrinsic and immune tumor microenvironment (iTME) factors associated with CAR T-cell efficacy, scRNAseq (10x Genomics V3.1) was performed on purified MM cells (CD138+) and associated iTME cells (CD138- mononuclear cells) from fresh bone marrow aspirates harvested prior to therapy in 13 patients treated at Moffitt Cancer Center. After biopsy, 7 of these patients were treated with ABECMA (idecabtagene vicleucel or ide-cel) and 6 were treated with ciltacabtagene autoleucel (cilta-cel or CARVYKTI®). Bone marrow biopsies were collected between 2021 and 2023. In addition to the molecular data, demographic information for the samples is provided. These data allow for the assessment of transcriptional signatures at the single-cell level in both the tumor and its bone marrow iTME, associated with CAR T-cell therapy in MM patients.

Study phs004878

Sequencing of Rare Pancreatic Tumors That Respond to PD-1 Blockade

Pancreatic cancer is nearly always refractory to immunotherapy, except in a rare subset of patients whose tumors have a high mutational burden (TMB), usually due to mismatch-repair deficiency. We collected tumors and matched blood from patients with pancreatic cancer, some of whom had high-TMB disease. We performed single-cell RNA-seq analyses of those samples to understand the correlates in the pancreatic tumor microenvironment of productive responses to immunotherapy. We found that different T cell populations responded to PD-1 blockade in TMB-high vs TMB-low tumors. This dataset consists of Illumina NovaSeq sequencing output (as FASTQ files) for blood and tumor libraries prepared using 10X Genomics Single Cell 5' Immune Profiling kits. FASTQs are provided for GEX, TCR, and (for multiplexed samples) HTO libraries.

Study phs004257

Incidental Detection of Maternal Neoplasia through Non-Invasive Cell-Free DNA Analysis (IDENTIFY), a Natural History Study

Prenatal cell-free (cf) DNA sequencing for fetal aneuploidy incidentally detects circulating tumor DNA in the plasma of asymptomatic pregnant women. Distinguishing the subset of women with malignant tumors detected by prenatal sequencing from those with benign conditions, such as uterine fibroids, is critical to maternal medical management. The Incidental Detection of Maternal Neoplasia Through Non-Invasive Cell-Free DNA Sequencing (IDENTIFY) study at the National Institutes of Health in Bethesda, MD, offers standardized cancer screening and cfDNA sequencing to asymptomatic or minimally symptomatic pregnant women with nonreportable prenatal cfDNA sequencing results. We previously reported that whole-body magnetic resonance imaging (WB-MRI) and a specific genome-wide sequencing pattern of chromosomal gains and losses involving three or more chromosomes could reliably differentiate which women had cancer. We continue to explore additional noninvasive biomarkers to identify the subset of women with nonreportable prenatal cfDNA sequencing results who have cancer and to predict tissues of origin, particularly when patients or their providers are reluctant to pursue diagnostic testing, WB-MRI studies are unavailable, or imaging findings are indeterminate. Here, cfDNA sequence analysis was performed to identify cancer driver somatic mutations that might aid in distinguishing between pregnant women who have a high likelihood of occult malignancy from those who do not. In this pilot study, prospectively collected blood samples from 65 pregnant or postpartum women with and without occult cancers were analyzed blindly for cfDNA somatic mutations in 275 cancer-associated genes.

Study phs004107

Cetuximab and Nivolumab in Recurrent/Metastatic Head and Neck Cancer

A multi-center, non-randomized, open label, phase I/II study was conducted at Moffitt Cancer Center, Ohio State University and Emory University. Early results of the clinical trial in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) has been previously published, showing that the combination of cetuximab and nivolumab has manageable toxicities and is more efficacious compared to the response rate of historical cetuximab or anti-PD-1 monotherapy (Chung et al., Cancers 2021, Chung et al., Clin Cancer Res 2022). Additional exploratory correlative studies were also conducted using the clinical specimens including formalin fixed paraffin embedded (FFPE) tumors and serially collected plasma cell free DNA (cfDNA; pre-treatment, on-treatment, and time of disease progression/end of treatment). These biomarker results were correlated with the clinical data obtained from the trial patients. Evaluated molecular biomarkers include DNA and RNA-sequencing and multiple immunohistochemistry markers. Altogether, our findings indicate that p16-negative R/M HNSCC patients may have greater benefit from the combination of cetuximab and nivolumab compared to patients with p16-positive HNSCC. It is anticipated that this resource will facilitate researchers to advance the therapeutic development by further understanding of HNSCC biology and provide tools to improve the clinical outcomes in incurable R/M HNSCC.

Study phs004268

Chromatin Accessibility Profiling Identifies a Stem Cell-Like Subtype of Small Cell Lung Cancer with Poor Prognosis

Eight-week-old male or female NSG mice (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ; #005557, Jackson Laboratory) were subcutaneously implanted with fresh patient needle biopsies. Mice were monitored daily, with caliper measurements and body weights performed twice weekly. Once tumors reached the size limit (2000 mm³) or mice became moribund, the mouse was euthanized, and a 3x3 mm³ tumor fragment was transplanted into a new mouse (P2). This process was repeated to achieve a minimum of passage three (P3) for each patient-derived origin. ATAC sequencing on PDX samples was conducted using the high-throughput Illumina HiSeq 4000 system. The same biopsy samples used for ATAC-seq were utilized for RNA-seq library preparation and sequencing, following the Illumina HiSeq protocol (NCI CCR Sequencing Facility). The study identified the stem cell subtype within Small Cell Lung Cancer (SCLC) cases and identified the gene signature associated with stemness behavior., which were validated in independent limited and extensive stage patients dataset.

Study phs003983

Molecular Profiling of Head and Neck Squamous Cell Carcinomas

This study performed targeted DNA sequencing of key NF-κB signaling pathway regulatory genes in matched tumor and normal tissues from patients with HPV-associated head and neck squamous cell carcinoma (HNSCC). A custom Ion Torrent AmpliSeq panel was designed to interrogate ten genes whose products regulate NF-κB activity and are frequently altered in the NF-κB-active subtype of HPV+ HNSCC: TRAF3, CYLD, TRAF2, NFKBIA, TNFAIP3, TRAF6, BIRC2, BIRC3, MYD88, and MAP3K14. The panel comprised 250 overlapping amplicons in a 2-primer pool format, achieving 93.65% coverage across the 24.86 kb target region. Genomic DNA was isolated from formalin-fixed paraffin-embedded (FFPE) macro-dissected tumor and matched normal tissues at the UNC Lineberger Comprehensive Cancer Center Translational Genomics Lab. This sequencing was performed as part of a study developing a clinical assay to identify HPV+ HNSCC subtypes defined by NF-κB activity for the purpose of risk stratification and de-escalation of radiation therapy.

Study phs004476

NCTN: Randomized Phase III Study of Maintenance Therapy With Bevacizumab, Pemetrexed, or a Combination of Bevacizumab and Pemetrexed Following Carboplatin, Paclitaxel and Bevacizumab for Advanced Non-Squamous NSCLC (E5508)

Study ID: E5508NCT Number: NCT01107626ECOG-ACRIN Cancer Research Group Submitted in collaboration with the NCTN/NCORP Data Archive Trial Title: NCTN: Randomized Phase III Study of Maintenance Therapy with Bevacizumab, Pemetrexed, or a Combination of Bevacizumab and Pemetrexed following Carboplatin, Paclitaxel and Bevacizumab for Advanced Non-Squamous NSCLC (E5508) Trial Description: RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of non-small cell lung cancer by blocking blood flow to the tumor. Pemetrexed disodium may stop the growth of tumor cells by blocking some enzymes needed for cell growth. It is not yet known whether giving bevacizumab or pemetrexed disodium alone or in combination is more effective in treating non-squamous non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying bevacizumab and pemetrexed disodium alone or in combination after induction therapy to see how well they work in treating patients with advanced non-squamous non-small cell lung cancer. Clinical data presented in the following publication(s): PMID 31361535 Disease type(s): Lung, Mediastinal and Pleural Neoplasm - Non-Small Cell Lung Cancer Clinical dataset(s) included: NCT01107626-D1 (PMID 31361535): There are two different datasets for PMID 31361535 from trial E5508. This dataset, NCT01107626-D1, contains baseline characteristics, treatment assignment, prior treatment, metastatic sites and efficacy data. Pemetrexed or bevacizumab is used for maintenance therapy of advanced no squamous non-small cell lung cancer (NSCLC). The combination of bevacizumab and pemetrexed has also demonstrated efficacy. This study contains two step registration, induction therapy step and maintenance therapy. All patients who were registered to at least one of the steps are included. Due to data cleaning efforts, data may contain slight discrepancies from that reported in Table 1 and Table 2 in the publication (PMID 31361535). The number of each metastatic site is incorrect in the publication: The data in this dataset is correct.NCT01107626-D2 (PMID 31361535): There are two different datasets for PMID 31361535 from trial E5508. This dataset, NCT01107626-D2, contains toxicity data. Pemetrexed or bevacizumab is used for maintenance therapy of advanced no squamous non‐small cell lung cancer (NSCLC). The combination of bevacizumab and pemetrexed has also demonstrated efficacy. This study contains two step registration, induction therapy step and maintenance therapy. All patients who were registered to at least one of the steps are included.You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

Study phs004240

NCTN: A Double-Blind Phase III Trial of Doxorubicin and Cyclophosphamide followed by Paclitaxel with Bevacizumab or Placebo in Patients with Lymph Node Positive and High Risk Lymph Node Negative Breast Cancer (E5103)

Study ID: E5103 NCT Number: NCT00433511ECOG-ACRIN Cancer Research GroupSubmitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: A Double-Blind Phase III Trial of Doxorubicin and Cyclophosphamide followed by Paclitaxel with Bevacizumab or Placebo in Patients with Lymph Node Positive and High Risk Lymph Node Negative Breast Cancer Trial Description: This randomized phase III trial studies doxorubicin hydrochloride, cyclophosphamide, and paclitaxel to see how well they work with or without bevacizumab in treating patients with cancer that has spread to the lymph nodes (lymph node-positive) or cancer that has not spread to the lymph nodes but is at high risk for returning (high-risk, lymph node-negative breast cancer). Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery and help prevent the tumor from returning. It is not yet known whether doxorubicin hydrochloride, cyclophosphamide, and paclitaxel are more effective with or without bevacizumab. You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication.Clinical data presented in the following publication(s): PMID 30040523PMID 30054636PMID 24584876Disease type(s): Breast Neoplasm - Breast Cancer - Invasive Clinical dataset(s) included: NCT00433511-D1 (PMID 30040523): There are three datasets for PMID 30040523 (-D1, -D2, and -D4). This dataset, NCT00433511-D1, contains baseline characteristics, treatment and follow up information, cardiac function measures, and efficacy data. Dataset NCT00433511-D2 contains toxicity data. Dataset NCT00433511-D4 contains updated time-to-event data that have undergone further data cleaning from those in NCT00433511-D1. NCT00433511-D2 (PMID 30040523): There are three datasets for PMID 30040523 (-D1, -D2, and -D4). This dataset, NCT00433511-D2, contains toxicity data. Dataset NCT00433511-D1 contains baseline characteristics, treatment and follow up information, cardiac function measures, and efficacy data. Dataset NCT00433511-D4 contains updated time-to-event data that have undergone further data cleaning from those in NCT00433511-D1.NCT00433511-D3 (PMID 30054636): This dataset, NCT00433511-D3, contains the data used to generate the results in PubMed ID PMID: 30054636; PMCID: PMC6385891, a non-primary publication from trial NCT00433511 looking at association of circulating tumor cells with late recurrence of ER+ breast cancer. Data include limited baseline characteristics, CTC results, time-to-recurrence data, and follow-up information. Data that are identical to those presented in NCT00433511-D1 (for the trial's primary publication, PMID 30040523) are not duplicated here in this dataset for NCT00433511-D3.NCT00433511-D4 (PMID 30040523): There are three datasets for PMID 30040523 (-D1, -D2, and -D4). This dataset, NCT00433511-D4, contains updated variables ttchf, ttbev, and os that have undergone further data cleaning from those in Dataset NCT00433511-D1 which corresponds to data used to generate the results for PMID 30040523. Dataset NCT00433511-D2 contains toxicity data.NCT00433511-D5 (Unpublished): Dataset NCT00433511-D5 contains data on time to local-regional recurrence and time to distant recurrence that were collected on the trial, but not published. NCT00433511-D6 (PMID 24584876): This dataset, NCT00433511-D6, contains the data published in PMID 24584876, a publication focusing on a subgroup of patients from ECOG-ACRIN trial E5103 (women who were premenopausal at enrollment, responded to the 12-month survey, had not undergone bilateral oophorectomy or ovarian function suppression before that survey, and had serum banked for research before chemotherapy). Data includes limited patient characteristics and amenorrhea indicators. Data that are identical to those presented in NCT00433511-D1 (for the trial's primary publication, PMID 30040523) are not duplicated in the NCT00433511-D6 dataset. Additional correlative data are available for this trial under phs003201.

Study phs004244

Genetic Factors Associated with Anthracycline-Induced Cardiomyopathy (COG-ALTE03N1)

We investigated the genetic mechanisms underlying anthracycline-induced cardiomyopathy, a serious long-term complication among childhood cancer survivors. We focused on the role of DNA damage response and repair (DDR) genes, which had not been previously studied in this context. A gene-based and pathway-based approach was applied to assess both the main effects and gene-by-anthracycline interaction effects of DDR genes on cardiomyopathy risk. The analysis was conducted using a matched case-control design within the COG-ALTE03N1 study, including 113 cases and 226 controls, all of whom were non-Hispanic White childhood cancer survivors exposed to anthracyclines. For each case, we randomly selected 1-3 childhood cancer survivors with no cardiomyopathy, matched on primary cancer diagnosis, year of diagnosis (±10y), and race/ethnicity. The selected controls had to have a longer duration of follow-up compared with time from cancer diagnosis to cardiomyopathy for the corresponding case. Participants provided blood or saliva for germline DNA isolation and genotyping. Genotyping was performed using Illumina HumanOmniExpress-12 v1.0 (709,358 SNPs) and IlluminaOmni5Exome-4 v1.3 arrays (4,293,368 SNPs), with merging of genotype data from the two arrays (683,781 overlapped SNPs) and quality control (QC) using PLINK. Of the 220 genes in the MD Anderson DDR gene website, 187 genes with 2,220 single nucleotide polymorphisms [SNPs] identified on our array data were included in the analyses. A total of 2,170 SNPs were retained in the final gene-based and pathway-based analysis in 339 anthracycline-exposed non-Hispanic White (NHW) patients (113 cases; 226 controls). Key findings included significant associations for FANCC and XRCC5 with cardiomyopathy risk (main effect), and a significant gene-environment interaction involving MGMT. The study also confirmed the involvement of DDR-related biological pathways through both genetic association and interaction analyses.Data Available Through dbGaP: • Genotype data (GWAS) for all study participants • Phenotype data: age at primary cancer diagnosis, sex, race/ethnicity, case-control status This dataset supports further research into genetic susceptibility to chemotherapy-induced adverse outcomes and enables cross-cohort comparisons in cardio-oncology.

Study phs003792

Cutaneous Squamous Cell Carcinoma: Integrating Germline and Somatic Alterations that Underlie Tumor Progression

Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in the United States, affecting over a million people annually, and with significant mortality due to metastasis. The overall scientific objective of this study is to identify and integrate novel tumor mutational data with previously characterized information on host genetic risk factors and clinical risk factors to better understand how cancer risk alleles contribute to the development of cSCCs capable of metastasis. We analyze 290 cSCCs (145 primary cSCCs) that progressed to metastasis and 145 non-metastatic primary cSCCs arising in the well characterized GERA cohort to provide a comprehensive landscape of genomic alterations in cSCCs. The aims of the study are: a) characterize the somatic genome and transcriptome of metastatic and non-metastatic cSCCs, b) integrate somatic mutational analysis with environmental exposure data, and c) develop a risk prediction tool for metastatic-cSCC that integrate genomic and clinical data.

Study phs003681

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