Search Results - EGA European Genome-phenome Archive

Childhood Cancer Data Initiative (CCDI): Metastatic Osteosarcoma Spatial Profiling

This study contains spatial transcriptional profiling of metastatic osteosarcoma specimens using the Visium platform. This work was done as part of the Childhood Cancer Data Initiative (CCDI).

Study phs003975

Pharmacokinetics and Pharmacogenomics of Ribociclib in Race-Based Cohorts (LEANORA)

Underrepresented populations' participation in clinical trials remains limited, and the potential impact of genomic variants on drug metabolism remains elusive. This study aimed to assess the pharmacokinetics (PK) and pharmacogenomics (PGx) of ribociclib in self-identified Black women with hormone receptor positive (HR+)/human epidermal growth factor receptor 2-negative (HER2) advanced breast cancer. LEANORA (NCT04657679) was a prospective, observational, multicenter cohort study involving 14 Black women. PK and PGx were evaluated using tandem mass spectrometry and PharmacoScan microarray. CYP3A5*3, CYP3A5*6, and CYP3A5*7 variants were genotyped and CYP3A5 phenotypes were constructed from these data. We observed 7 poor metabolizers (PM), 6 intermediate metabolizers (IM), and one normal metabolizer (NM). The area under the curve of plasma concentration versus time curve (AUC) of ribociclib did not differ between PMs (39,230 hr*ng/mL) and IM/NMs (43,546 hr*ng/mL; P=0.38). The incidence of adverse events (AEs) was also similar. We found no association between CYP3A5 genotype and ribociclib exposure. Continued efforts are needed to include diverse populations in clinical trials to ensure equitable treatment outcomes.

Study phs003770

Intratumoral Heterogeneity and Clonal Evolution Induced by HPV Integration

The human papillomavirus (HPV) genome is integrated into host DNA in most HPV-positive cancers, but the consequences for chromosomal integrity are unknown. We used continuous long-read sequencing of oropharyngeal cancers and cervical cancer cell lines to resolve structural variation induced by HPV. We discovered a previously undescribed form of structural variation, "heterocateny," characterized by diverse, interrelated, and repetitive patterns of concatemerized virus and host DNA segments within a cancer.

Study phs003396

NCTN: EVEREST: EVErolimus for Renal Cancer Ensuing Surgical Therapy, A Phase III Study (S0931)

Study ID: S0931 NCT Number: NCT01120249 SWOG Cancer Research Network Submitted in collaboration with the NCTN/NCORP Data Archive Trial Title: NCTN: EVEREST: EVErolimus for Renal Cancer Ensuing Surgical Therapy, a Phase III Study (S0931) Trial Description: RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. PURPOSE: This phase III trial is studying everolimus to see how well it works in treating patients with kidney cancer who have undergone surgery. Clinical data presented in the following publication(s): PMID 37524096 Disease type(s): Kidney Neoplasm - Renal Cell Carcinoma Clinical Dataset(s) included: NCT01120249-D1 (PMID 37524096): There are two datasets for S0931's primary publication 37524096 (-D1 and -D2). The clinical dataset contains patient-level data (one row per patient), including eligibility, evaluability, treatment, demographic, baseline information, stratification factors, and unblinding. It also contains survival, cause of death, recurrence site, biopsy, and dose modification data. NCT01120249-D2 (PMID 37524096): There are two datasets for S0931's primary publication 37524096 (-D1 and -D2). This toxicity dataset contains event-level information (one row per patient per adverse event experience on trial). 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 phs004249

Germline Mutations and Developmental Mosaicism Underlying EGFR-Mutant Lung Cancer

We designed this study to examine the etiology of multiple lung tumors in EGFR-mutant non-small cell lung cancer patients who undergo surgical resection. Participants were 52-85 years old never or former smokers, who had at least 2 surgical lung tumor pathology specimens available in the Massachusetts General Hospital biobank, at least one of which had an EGFR mutation by routine clinical genotyping. 10 patients were selected, along with two patients from a family with an inherited EGFR-T790M mutation leading to multiple lung tumors. These patient tumor samples and matched normal lung samples were microdissected to collect DNA.In addition to obtaining clinical histories, we performed whole exome sequencing to evaluate the genetic profile of matched tumor and normal samples. The WES data are available on dbGaP. Our data showed increasing mutational burden and copy number alteration with increasing invasiveness, as compared to normal tissues, for the subset of samples that were assessed for tumor invasiveness. We also observed a range of numbers of shared mutations between tumors in a single patient, indicating different degrees of relatedness between lung tumors. We hope that this resource will help researchers understand non-small cell lung cancer presentations with multiple lung tumors. These data may aid in clinical decision making for such patients.

Study phs003379

Mayo Clinic - Fecal Microbiota and Adenomas

Background: Adenomatous polyps are the most common precursor to colorectal cancer (CRC), the second leading cause of cancer death in the United States. We sought to learn more about early events of carcinogenesis by investigating shifts in the gut microbiota of patients with adenomas. Methods: We analyzed 16S rRNA gene sequences from the fecal microbiota of patients with adenomas (n=233) and without (n=547). Results: Multiple taxa were significantly more abundant in patients with adenomas, including Bilophila, Desulfovibrio, pro-inflammatory bacteria in the genus Mogibacterium, and multiple Bacteroidetes species. Patients without adenomas had greater abundances of Veillonella, Firmicutes (Order Clostridia), and Actinobacteria (family Bifidobacteriales). Many of our findings were consistent with previously reported shifts in the gut microbiota of CRC patients. Importantly, the altered adenoma profile is predicted to increase primary and secondary bile acid production, as well as starch, sucrose, lipid, and phenylpropanoid metabolism. Conclusions: These data suggest that diets rich in refined sugar, protein, and lipids may lead to increased bile acid production, creating a colonic environment that promotes the growth of bile-tolerant microbes such as Bilophilia and Desulfovibrio. In turn, these microbes may produce genotoxic or inflammatory metabolites such as H2S and secondary bile acids, catalyzing adenoma development and eventually CRC. Impact: This study suggests a plausible biological mechanism to explain the links between diet, shifts in the microbiota, and CRC. This represents a first step toward resolving the complex interactions that shape the adenoma-carcinoma sequence of CRC and may facilitate personalized therapeutics focused on the microbiota.

Study phs001204

Oncogenome of Kaposi Sarcoma

Kaposi Sarcoma (KS) is an aggressive cancer caused by the Kaposi Sarcoma Herpesvirus (KSHV/HHV-8). Individuals with immunodeficiencies, exemplified by HIV, have an elevated risk of developing KS. However, understanding of the genetic factors contributing to KS progression is still limited. To explore potential genetic alterations in KS that could offer biological or therapeutic insights, whole exome sequencing was performed on 78 KS tumors and matching normal skin samples from 59 adults with KS (46 with HIV-associated KS and 13 with HIV-negative KS) receiving treatment at the Uganda Cancer Institute in Kampala, Uganda. Results showed a very low mutational burden in all samples except one (median = 11 mutations), which is the smallest number of mutations found across all 33 cancer types in The Cancer Genome Atlas (TCGA). No recurrent mutations were identified. Mutational signatures included impaired DNA mismatch repair and smoking. There was no evidence suggesting that multiple tumors from the same patient originated from a single clone. The number of genome copy alterations per genome was higher in tumors from individuals without HIV and those with advanced-stage disease. This suggests that lesions that take longer to develop may accumulate more alterations, although the overall number of alterations remains low compared to other cancers. These findings suggest that KS pathogenesis differs from other cancers, with KSHV viral infection and the expression of viral oncogenes being the primary drivers of carcinogenesis, rather than clonal oncogenic transformation arising from genetic alterations of cancer-related cellular genes.

Study phs003897

Childhood Cancer Data Initiative (CCDI): Admixture Analysis of Acute Lymphoblastic Leukemia in African American Children: The ADMIRAL Study

Children with substantial African ancestry are observed to have less than half the incidence of B-cell acute lymphoblastic leukemia (B-ALL) than children of other continental ancestries. The Admixture Analysis of Acute Lymphoblastic Leukemia in African American Children study (ADMIRAL) was designed to investigate genes and loci that explain the unique risk profile of African American children. Germline DNA samples were obtained from Children's Oncology Group frontline protocols, the Michigan BioTrust for Health, and various academic hospital ALL banks. Cases represented a diagnosis of B-ALL between the ages of 0-20 years, and controls were matched on birth year, sex, and maternal race/ethnicity. All participants have reported Black/African American race or substantial inferred African genetic ancestry. Altogether, 840 cases and 392 internal controls are included in this submission. All samples were genotyped on the Illumina Global Diversity Array 8v1. Phenotype information includes case/control status and reported sex.

Study phs004222

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

CIDR: Elucidating Epigenetic Mechanisms of Racial/Ethnic Disparities in Pancreatic Cancer

This is a nested case-control study of 689 pancreatic cancer cases and 807 matched controls from the Multiethnic Cohort Study (MEC) (see dbGaP phs002183), a diverse prospective cohort of >215,000 African American, European American, Japanese American, Latino, and Native Hawaiian individuals from Hawaii and Los Angeles. The objective of this study is to identify blood DNA methylation markers of pancreatic cancer susceptibility and to examine whether epigenetics can partially explain the racial and ethnic disparities of pancreatic cancer. Our specific aims are: 1) to identify multiethnic epigenetic markers of pancreatic cancer risk, 2) to assess whether epigenetics improves the prediction of pancreatic cancer across race and ethnicity, and 3) to evaluate whether epigenetics mediates the association between known modifiable risk factors and pancreatic cancer. The findings from this study are expected to identify potential ethnic-specific carcinogenic processes and elucidate the determinants of racial and ethnic disparities in pancreatic cancer.

Study phs003735

NCTN: A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT Vs AS and 3DCTR/IMRT Followed by Chemotherapy with Docetaxel and Prednisone for Localized, High-Risk, Prostate Cancer (RTOG-0521)

Study ID: RTOG-0521 NCT Number: NCT00288080 NRG Oncology Submitted in collaboration with the NCTN/NCORP Data Archive Trial Title: NCTN: A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT vs AS and 3DCTR/IMRT followed by Chemotherapy with Docetaxel and Prednisone for Localized, High-Risk, Prostate Cancer (RTOG-0521) Trial Description: RATIONALE: Androgens can cause the growth of prostate cancer cells. Hormone therapy using drugs, such as leuprolide, goserelin, flutamide, or bicalutamide, may fight prostate cancer by lowering the amount of androgens the body makes. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving hormone therapy and radiation therapy together with chemotherapy is more effective than giving hormone therapy together with radiation therapy in treating prostate cancer. PURPOSE: This randomized phase III trial is studying hormone therapy and radiation therapy followed by docetaxel and prednisone to see how well it works compared to hormone therapy and radiation therapy in treating patients with localized prostate cancer. Clinical data presented in the following publication(s): PMID 30860948Disease type(s): Reproductive System Neoplasm, Male - Prostate Cancer Clinical Dataset(s) included: NCT00288080-D1 (PMID 30860948): This dataset, NCT00288080-D1, contains the data presented in the RTOG-0521 primary publication (PMID: 30860948). The dataset includes reasons for exclusion, treatment arm, baseline characteristics, treatment compliance, adverse event, survival, cause of death, biochemical failure, and distant metastases data. 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 phs004255

P4HA1 Mediates Hypoxia-Induced Invasion in Human Pancreatic Cancer Organoids

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy defined by extensive invasion into the local tumor microenvironment and systemic metastasis. PDAC develops in a hypoxic microenvironment and adapts to survive under low oxygen conditions, including the activation of processes that may enhance the ability of cancer cells to invade locally or metastasize. Here we employ bulk RNA-sequencing of eight patient-derived organoid (PDO) cultures grown in hypoxia and normoxia to identify differentially expressed genes. PDOs were grown in Matrigel, transferred into collagen domes, then incubated in hypoxia or normoxia. Invasive organoids were individually collected from collagen domes grown in hypoxia and normoxia separately and processed for RNA-sequencing analysis. Using this dataset, prolyl 4-hydroxylase subunit alpha (P4HA1) was identified as a potential regulator of PDAC invasion in hypoxia. This dataset exists as a reference for gene expression of invasive organoids in hypoxia and normoxia.

Study phs003961

Utility of Pancreatic Tumor Scrapings for Organoid Development and Precision Medicine Strategies

Patient-derived organoids (PDOs) hold promise for predicting individualized drug responses, but their establishment is often constrained by the limited availability of tumor material and prior neoadjuvant treatment. Standard PDO generation relies on dissected tissue slices from the cut surface of the tumor which may include both the invasive front, where it is postulated that more aggressive cancer cells reside, and potentially fewer viable neoplastic cells in the tumor center. This study investigates whether scraping the PDAC cut surface is a feasible method for PDO establishment compared to standard tissue samples, in order to take advantage of the potential harvesting of viable neoplastic cells from the invasive front. Tumor scrapings from 26 patients and matched tissue slices from 20 patients were collected. PDOs were successfully established from 10 tumor scrapings and 8 matched tissue slices, including 3 neoadjuvant-treated cases. Organoid histologic architecture was comparable to the surgical tumor specimens, with paired scraping and tissue slice PDOs showing genomic and transcriptomic concordance. Pharmacotyping demonstrated that scraping PDOs reliably captured patient-specific chemosensitivity, highlighting the potential for a viable alternative method to standard tissue slice PDOs. As proliferative and treatment-resistant neoplastic cells often originate from the tumor edge, increasing representation of the periphery and across the tumor may offer a more comprehensive model of invasive tumor biology, improving the clinical and research utility of PDOs.

Study phs004385

Randomized Phase 2 Study of Neoadjuvant Chemotherapy, Carboplatin and Paclitaxel, with or without Atezolizumab in Triple Negative Breast Cancer (TNBC)

This phase II trial studies how well carboplatin and paclitaxel, with or without atezolizumab, before surgery works in treating patients with newly diagnosed, stage II-III triple negative breast cancer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin 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. Giving carboplatin and paclitaxel with or without atezolizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Study phs003296

Investigations of Genetic Variation in Families Affected by MUTYH-Associated Polyposis

Defects in the Base-Excision Repair gene, MUTYH, are known to increase colorectal cancer risk through a recessive Mendelian pattern and raise mutation rates in both normal somatic and germline mammalian cells. In this study, we employed whole genome sequencing (WGS) of fifteen human individuals (representing 4 related families) at 50X coverage to examine germline de novo mutation rates in a large family with pathogenic MUTYH mutations and a history of colorectal cancer. We used an in vitro cell line assay to determine the family's genotype (p. Y179C/V234M, transcript NM_001128425) partially attenuates MUTYH's function. The children of mothers affected by the biallelic pathogenic genotype were associated with a moderate increase in the C>A mutation rate, but this effect was determined to be lower than previously reported mutator effects for other biallelic pathogenic MUTYH genotypes. No similar mutation rate increase was found in children of fathers with the same genotype despite calculating that we should have adequate power to detect such a mutator effect, indicating that MUTYH's role in repairing oxidative stress might be more significant in female reproductive aging than in males. We used a combination of in vitro cell line assays and bioinformatics pipelines to assess the impact of the MUTYH genotype on germline mutation rates. The study design ensures that sufficient statistical power was available to detect mutator effects in both maternal and paternal lineages. The sequencing data generated from this study include single sample genotype files derived from WGS, focusing on germline DNA. The phenotypic data at individual level and sequence data can be accessed by authorized users, facilitating further exploration of the relationship between MUTYH pathogenic variants and colorectal cancer risk.

Study phs003554

NCTN: Treatment of Children with All Stages of Hepatoblastoma with Temsirolimus (NSC#683864) Added to High Risk Stratum Treatment (AHEP0731)

Study ID: AHEP0731 NCT Number: NCT00980460Children's Oncology Group (COG) Submitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: Treatment of Children with All Stages of Hepatoblastoma with Temsirolimus (NSC#683864) Added to High Risk Stratum Treatment (AHEP0731)Trial Description: This phase III trial studies the side effects and how well risk-based therapy works in treating younger patients with newly diagnosed liver cancer. Surgery, chemotherapy drugs (cancer fighting medicines), and when necessary, liver transplant, are the main current treatments for hepatoblastoma. The stage of the cancer is one factor used to decide the best treatment. Treating patients according to the risk group they are in may help get rid of the cancer, keep it from coming back, and decrease the side effects of chemotherapy. Clinical data presented in the following publication(s): PMID 28211941PMID 30975630 PMID 34762296PMID 35810020PMID 37073741Disease type(s): Gastrointestinal Neoplasm - Liver and Hepatobiliary Cancer Clinical Dataset(s) included: • NCT00980460-D1 (PMID 28211941): There are three datasets (-D1 through -D3) for the AHEP0731 publication 28211941, reporting on the high-risk cohort who received Vincristine and Irinotecan. This dataset provides the information for baseline characteristics, PRETEXT grouping, surgery details, changes in AFP levels, response, relapse site, and surgical outcome plus event-free and overall survival for all evaluable patients as reported in the manuscript. Information is only provided for evaluable patients (analysiset = 1). Variables were left blank for the patients who were not evaluable (analysiset = 0). There is one row per patient. NCT00980460-D2 and -D3 contain toxicity data for this high-risk cohort. • NCT00980460-D2 (PMID 28211941): There are three datasets (-D1 through -D3) for the AHEP0731 publication 28211941, reporting on the high-risk cohort who received Vincristine and Irinotecan. This dataset provides the information for the specific toxicities that occurred during cycles 1 through 10 for evaluable patients. Evaluable patients are defined in NCT00980460-D1 (analysiset = 1). There are multiple rows per patient depending on whether they had multiple cycles submitted. NCT00980460-D1 contains baseline characteristics and outcome data and NCT00980460-D3 contains nausea and neuropathy toxicity events for this high-risk cohort. • NCT00980460-D3 (PMID 28211941): There are three datasets (-D1 through -D3) for the AHEP0731 publication 28211941, reporting on the high-risk cohort who received Vincristine and Irinotecan. This dataset provides the information for nausea and neuropathy that occurred during cycles 1 and 2 for evaluable patients. Evaluable patients are defined in NCT00980460-D1 (analysiset = 1). There is one row per patient. NCT00980460-D1 contains baseline characteristics and outcome data and NCT00980460-D2 contains toxicities from cycles 1 through 10 for this high-risk cohort. • NCT00980460-D4 (PMID 30975630): There are two datasets (-D4 and -D5) for the AHEP0731 publication 30975630, reporting on the low-risk cohort. This dataset provides the information for eligibility, baseline characteristics, disease stage, PRETEXT grouping, surgery details, changes in AFP levels, surgical outcome event-free survival, and overall survival. Information is only provided for eligible patients (analysis01 = 1). There is one row per patient. NCT00980460-D5 contains toxicity data for the low-risk cohort. • NCT00980460-D5 (PMID 30975630): There are two datasets (-D4 and -D5) for the AHEP0731 publication 30975630, reporting on the low-risk cohort. This dataset provides the information for the specific toxicities that occurred during protocol therapy. Evaluable patients are defined in NCT00980460-D4 (analysis01 = 1). There is one row per patient/toxicity term. Each row has the maximum grade of the particular toxicity term observed during the patient's protocol treatment. NCT00980460-D4 contains baseline characteristics and outcome data for the low-risk cohort. • NCT00980460-D6 (PMID 34762296): There are three datasets (-D6 through -D8) for the AHEP0731 publication 34762296, reporting on the intermediate-risk cohort. This dataset provides the information for all intermediate-risk patients who were enrolled on AHEP0731, up to 02/10/2020, both eligible and ineligible. It contains data presented in Figure 1 (the consort diagram), Figure 2 (Event-Free and Overall Survival of Patients with Unresectable non-Metastatic Hepatoblastoma), Table 1 (Patient Demographics for Patients with Intermediate-risk Hepatoblastoma), and the baseline characteristics, relapse sites, PRETEXT grouping, changes in AFP levels, surgery type, and evaluability for toxicity analyses. There is one row per patient. There are 105 patients in this dataset. NCT00980460-D7 contains mean percentage of target dose delivered data and NCT00980460-D8 contains toxicity data for the intermediate-risk cohort. • NCT00980460-D7 (PMID 34762296): There are three datasets (-D6 through -D8) for the AHEP0731 publication 34762296, reporting on the intermediate-risk cohort. This dataset, NCT00980460-D7, provides the information for all eligible intermediate-risk patients enrolled on AHEP0731, up to 02/10/2020. It contains data on the mean percentage of the target dose delivered for chemotherapy. There are 195 observations in this dataset, multiple rows per patient, with proportion of target dose delivered for cisplatin, 5-FU, doxorubicin and vincristine. NCT00980460-D6 contains baseline characteristics and outcome data and NCT00980460-D8 contains toxicity data for the intermediate-risk cohort. • NCT00980460-D8 (PMID 34762296): There are three datasets (-D6 through -D8) for the AHEP0731 publication 34762296, reporting on the intermediate-risk cohort. This dataset, NCT00980460-D8, provides the information for adverse events recorded for all eligible intermediate-risk patients enrolled on AHEP0731, up to 02/10/2020. It contains data on Table 2 (Toxicities (Grade 3, 4, and 5) of Patients with Intermediate-risk Hepatoblastoma), and the information on adverse events and toxicities in the Results section of the manuscript. There are 723 observations, one for each toxicity type per patient per cycle, included in this dataset. The number of rows per patient is dependent on the number of adverse events submitted. NCT00980460-D6 contains baseline characteristics and outcome data and NCT00980460-D7 contains mean percentage of target dose delivered data for the intermediate-risk cohort. • NCT00980460-D9 (PMID 35810020): There is one dataset for the AHEP0731 publication 35810020, reporting on the very low-risk cohort. NCT00980460-D9 provides the information for the 8 very low-risk hepatoblastoma patients who were enrolled on AHEP0731. The dataset contains baseline characteristics, α-fetoprotein levels, pretext group, vascular involvement, surgical details and tumor histology from local and central review, as well as outcome data as reported in the manuscript. It is used to generate all the tables in the manuscript, (Table 1. Patient Characteristics for Children with Very Low-Risk Hepatoblastoma and Table 2. Clinical and Surgical Traits for Children with Very Low-Risk Hepatoblastoma), and Figure 2. Event-free Survival and Overall Survival of Patients with Very Low Risk Hepatoblastoma Resected at Diagnosis. There are 8 patients in this dataset. There is one row for each patient. • NCT00980460-D10 (PMID 37073741): There are two datasets (-D10 and -D11) for the AHEP0731 publication 37073741, reporting on the high-risk cohort who received Vincristine, Irinotecan, and Temsirolimus. This dataset, NCT00980460-10, provides the information of baseline characteristics, α-fetoprotein levels, α-fetoprotein and RECIST response, as well as details on recurrent disease, metastatic disease, and surgery for the 40 high-risk hepatoblastoma patients who were enrolled on AHEP0731. Tumor histologic information and pretext classification from central review are also included as well as outcome data as reported in the manuscript. It is used to generate Table 1. Characteristics of eligible patients with high-risk hepatoblastoma treated with upfront vincristine/irinotecan/temsirolimus window therapy, Table 2. Response of patients to upfront vincristine/irinotecan/temsirolimus window therapy, Table 3. Surgical outcomes for patients treated with vincristine/irinotecan/temsirolimus upfront window therapy, Figure 1. Alpha-fetoprotein (AFP) decline after two cycles of VIT (vincristine/irinotecan/temsirolimus) therapy, and Figure 2. Event-free and overall survival of patients with high-risk hepatoblastoma treated with VIT (vincristine/irinotecan/temsirolimus). There are 40 patients in this dataset. There is one row for each patient. NCT00980460-D11 contains toxicity data for this high-risk cohort. • NCT00980460-D11 (PMID 37073741): There are two datasets (-D10 and -D11) for the AHEP0731 publication 37073741, reporting on the high-risk cohort who received Vincristine, Irinotecan, and Temsirolimus. This dataset, NCT00980460-D11, provides all grade 3 and 4 adverse events while on protocol therapy for the 36 eligible high-risk hepatoblastoma patients enrolled on AHEP0731 (Supplemental Table 3. Selected Grade 3 and 4 Toxicities) as well as selected grade 3 and 4 adverse events while on protocol therapy (Table 4. Selected grade 3 and 4 toxicities for patients treated with vincristine/irinotecan/temsirolimus upfront window therapy followed by cisplatin/5-fluorouracil/vincristine/doxorubicin.). The number of rows per patient is dependent on the number of adverse events submitted. NCT00980460-D10 contains baseline characteristics and outcome data for this high-risk cohort. 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 phs004135

The Vaginal Microbiome, Maternal Response, and Preterm Birth

An estimated 13 million preterm births (PTBs) occur annually worldwide, and PTB is the single most significant contributing factor to neonatal morbidity and mortality. Mechanisms underlying PTB are unknown hampering development of effective prediction and prevention strategies. PTB is linked to local and distant infections and recent data suggests that vaginal bacterial microbiome early in pregnancy is associated with subsequent PTB. Viral infections behave differently during pregnancy, with common viral infections such as varicella and influenza causing much more severe disease during pregnancy and human papillomavirus, the causative virus in cervical cancer, associated with a 2-fold increased risk for PTB. However, comprehensive assessment of vaginal viral communities during pregnancy has not been performed. Lastly, although maternal inflammation is one of the leading triggers for PTB, the precise constellation of inflammatory signals is not known. We propose that examining microbial communities or host response alone is incomplete, but that their combination will lead to refined definitions of appropriate and inappropriate microbe-maternal biology and shed new light on the old problem of PTB. Our central hypothesis is that PTB can be estimated by a combination of three criteria: vaginal bacterial communities, vaginal eukaryotic viral communities, and maternal inflammatory response. We have an interdisciplinary team assembled including perinatologists, epidemiologists, virologists, and genomics informatics experts, leveraging the unique capabilities of The McDonnell Genome Institute at Washington University in St. Louis, a well-established pregnancy bio-specimen and clinical data infrastructure, and a high-PTB burdened racially diverse patient population to test this novel hypothesis. The aims of this project are: 1) to determine the ability of bacterial and viral communities in the vagina and their dynamics over time to predict PTB, and 2) to determine the ability of the host inflammatory response in the vagina in the context of microbial communities to predict PTB. The proposed research is innovative, for the first time, comprehensively characterizing the eukaryotic vaginal virome simultaneously with vaginal bacterial communities and longitudinally capturing the maternal response to these communities. We employ an efficient study design, a well-established research infrastructure, and renowned genome sequencing expertise to test a physiologically plausible but uninvestigated paradigm that bacterial and viral communities in concert with the maternal host response can predict PTB.

Study phs003875

A Translational, Pharmacodynamic and Pharmacokinetic Phase IB Clinical Study of Everolimus in Resectable Non-Small Cell Lung Cancer

This phase IB clinical trial studied the pharmacodynamic changes induced by everolimus in patients with previously untreated, resectable non small cell lung cancer. Using a combination of in vivo and ex vivo assessments with FDG PET, immunohistochemistry and genomic assays, evidence of mTOR pathway perturbation was assessed in patients treated with everolimus, an allosteric mTOR inhibitor. Untreated patients served as controls for comparison. Key results from this work include a dose-dependent biologic effect of everolimus, signal of activity in RAS mutant tumors as well as near complete metabolic and pathologic response in a case of sarcomatoid lung cancer. These findings represent novel translational insights that can guide future development of mTOR inhibitors in lung cancer and other tumor types. Additionally, metabolic response and anatomic tumor shrinkage observed in a significant proportion of patients following a short of duration of therapy with everolimus suggests potential clinical utility of this agent in carefully-selected lung cancer patients.

Study phs000829

Health Information National Trends Survey-SEER (HINTS-SEER)

HINTS-SEER is a cross-sectional survey that sampled cancer survivors from three different SEER cancer registries. Sampling frames of survivors from each registry were stratified by time since diagnosis and race/ethnicity, with non-malignant tumors and non-melanoma skin cancers excluded. Respondents who consented completed a self-administered questionnaire sent through the mail and resulted in a total sample of 1,234 respondents. The goal of HINTS-SEER was to better understand the communication needs and practices, information preferences, risk behaviors and cancer knowledge of cancer survivors using a modified version of the Health Information National Trends Survey (HINTS) specifically designed for cancers survivors. Demographic information on the survivors showed that over 60% of the sample was 10 or more years since diagnosis with the most common cancers being male reproductive (24.6%), female breast (23%) and melanoma (9.6%) and gastrointestinal (8.6%). De-identified data is available in SAS, SPSS, and STATA formats, as part of a data package that also includes a history document, methodology report, data analysis recommendations, and a codebook.

Study phs004065

Center for Common Disease Genomics (CCDG) - Cardiovascular: Multiethnic Cohort

The genetic basis of cardiovascular disease in individuals of non-European ancestry remains largely unknown. Availability of ethnically diverse study populations is essential to investigate the underlying causes of disease.The National Human Genome Research Institute (NHGRI) has funded the Centers for Common Disease Genomics (CCDG), a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to multiple common disease phenotypes and to better understand the general principles of genomic architecture underlying common, complex, inherited diseases. The Multiethnic Cohort (MEC) of the University of Hawaii Cancer Center and the University of Southern California comprises primarily five ethnic groups: Caucasians, Japanese Americans, Native Hawaiians, African Americans and Latinos. This study contains whole genome sequence data derived from participants in the MEC cohort identified as having early onset coronary artery disease.

Study phs003499

Proteogenomic Studies to Understand Mechanisms and Drivers of Resistance to Immunotherapies

Immune checkpoint inhibitors (ICIs) targeting programmed death (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) produce durable responses in advanced cutaneous melanoma, yet reliable predictive biomarkers remain elusive. We performed a multi-cohort proteogenomic investigation of pre-treatment formalin-fixed paraffin-embedded (FFPE) biopsies from patients with metastatic cutaneous melanoma who later underwent either dual PD-1+CTLA-4 ICI therapy or PD-1 ICI monotherapy. Melanoma metastases of the lung, lymph node, and skin from the 3 cohorts were collected from 12 study sites in the United States, Europe, and Australia, comprising two separate PD-1+CTLA-4 ICI-treated discovery and validation cohorts ("Discovery Cohort" and "Validation Cohort 1", n=164 samples), and one PD-1 ICI monotherapy-treated validation cohort ("Validation Cohort 2", n=44 samples). Comprehensive genomic profiling was performed across the Discovery and two Validation Cohorts (across 180 individual samples) using Ribo-Erase total RNA sequencing (RNA-seq) (data generated for 173 samples), low-pass whole-genome sequencing (lpWGS) for the purpose of detecting somatic copy-number alterations (data generated for 177 samples), and a custom melanoma-focused targeted DNA sequencing panel (comprised of 86 genes, ~0.75Mb) designed to maximize the sensitivity of detecting recurrent and clinically actionable mutations (data generated for 175 samples). Pathway-level proteomic clustering identified three tumor subtypes; ICI-sensitive (immune-inflamed), ribosome-high (translationally active), and epithelial-mesenchymal transition (EMT)-like (stromal-enriched) that were reproducibly validated and showed significant PFS differences (p = 0.02–0.03) across cohorts. Subtype–outcome associations were consistent with previous immunotherapy datasets, with pooled hazard ratios ~0.5–0.8 for immune-enriched tumors. Additionally, we identified a 127-protein classifier that outperformed previously reported genomic signatures, suggesting that proteomic subtyping captured clinically relevant biology not accessible via genomics or transcriptomics alone. Our results identify potential new therapeutic vulnerabilities and lay the foundation for biomarker-driven patient stratification in combination ICI trials. Proteomic data will be made available through the National Cancer Institute's Proteomic Data Commons repository.

Study phs004511

A Therapeutic Vaccine for Fibrolamellar Hepatocellular Carcinoma

Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of liver cancer affecting 33 children and young adults that is driven by a chimeric protein, DNAJ-PKAc. We conducted a phase 1 clinical trial of a therapeutic vaccine targeting DNAJ-PKAc 38 (FLC-Vac), in combination with nivolumab and ipilimumab, in children and adults with advanced FLC. Among 16 patients enrolled, 12 completed the vaccine priming phase and were evaluable for both immunological and clinical endpoints. Grade 3 treatment-related adverse events were reported by six patients (37.5%). DNAJ43 PKAc-specific T cell responses were detected in 9/12 patients after treatment. In the subset of patients who completed the initial priming phase the disease control rate (DCR) was 75% (9/12), with three partial responses (25%). All patients with clinical responses also had DNAJ-PKAc specific T cell responses, from which we identified multiple class II-restricted T cell receptors (TCRs) with specificity for DNAJ-PKAc. Correlates of response included both functional neoantigen reactivity and changes in TCR repertoire features over time. Immune escape in two patients corresponded with immune exhaustion rather than neoantigen escape or HLA loss.

Study phs003970

NCTN: A Phase III Randomized Trial of Adjuvant Chemotherapy With or Without Bevacizumab for Patients With Completely Resected Stage IB (>= 4 cm) - IIIA Non-small Cell Lung Cancer (NSCLC) (E1505)

Study ID: E1505NCT Number: NCT00324805ECOG-ACRIN Cancer Research Group Submitted in collaboration with the NCTN/NCORP Data Archive Trial Title: NCTN: A Phase III Randomized Trial of Adjuvant Chemotherapy with or without Bevacizumab for Patients with Completely Resected Stage IB (>= 4 cm) - IIIA Non-small Cell Lung Cancer (NSCLC) (E1505) Trial Description: This randomized phase III trial studies chemotherapy and bevacizumab to see how well they work compared to chemotherapy alone in treating patients with stage IB, stage II, or stage IIIA non-small cell lung cancer that was removed by surgery. Drugs used in chemotherapy 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. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab also may stop the growth of non-small cell lung cancer by blocking the growth of new blood vessels necessary for tumor growth. It is not yet known whether chemotherapy is more effective with or without bevacizumab in treating non-small cell lung cancer. Clinical data presented in the following publication(s): • PMID 29129443 Disease type(s): Lung, Mediastinal and Pleural Neoplasm - Non-Small Cell Lung Cancer Clinical dataset(s) included: • NCT00324805-D1 (PMID 29129443): There are four different datasets for PMID 29129443 (trial NCT00324805). This dataset, NCT00324805-D1, contains baseline characteristics, stratification factors, treatment, resection type, site of recurrence, and efficacy data. • NCT00324805-D2 (PMID 29129443): There are four different datasets for PMID 29129443 (trial NCT00324805). This dataset, NCT00324805-D2, contains grade 2 toxicity data presented in Table 2 of the manuscript. • NCT00324805-D3 (PMID 29129443): There are four different datasets for PMID 29129443 (trial NCT00324805). This dataset, NCT00324805-D3, contains grades 3-5 toxicity data presented in Table 3 of the manuscript. • NCT00324805-D4 (PMID 29129443): There are four different datasets for PMID 29129443 (trial NCT00324805). This dataset, NCT00324805-D4, contains worst grade toxicity information and can be used to derive the number of patients with worst degree 1/2 toxicities (bottom row of Table 2); and the worst degree grade 3-5 events in Table 3 and Supplement. 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 phs004246

A Phase Ib Study of Sapacitabine and Olaparib in Patients With BRCA1/2-Mutated (BRCA1/2m) Metastatic Breast Cancer

PARP inhibitors significantly extend progression-free survival (PFS), compared to chemotherapy in patients with germline BRCA1/2 (gBRCA1/2)-mutated HER2-negative metastatic breast cancer, but responses are not durable. Preclinical studies suggest that sapacitabine, an oral nucleoside analog, is synergistic with PARP inhibition in cell lines harboring homologous recombination repair (HRR) defects. To translate these findings, this phase Ib study combining sapacitabine and olaparib enrolled ten patients with gBRCA1/2-mutated HER2-negative metastatic breast cancer. The recommended phase 2 dose was not determined due to hematological toxicities, mainly neutropenia and anemia. Archival tumors from responders demonstrated evidence of HRR deficiency or of high replication stress. At progression, BRCA1/2 reversion mutations associated with a microhomology-mediated end-joining (MMEJ) signature and other acquired putative non-reversion mechanisms of resistance were identified. The median PFS observed of 9.7 months, with three patients experiencing clinical benefit greater than 15 months, suggests that the addition of sapacitabine to PARP inhibition merits further investigation.

Study phs004095

Evaluation of the Effects of Endocrine Therapy and Abemaciclib on Host and Tumor Immune Cell Repertoire/Function in Advanced ER+/HER2- Breast Cancer

To characterize the advanced and metastatic breast tumor immune landscape and the impact of CDK4/6 inhibition on its composition and function, we used scRNA-seq to analyze tumor biopsies pre- and post- treatment with ET and the CDK4/6i, abemaciclib. Patients with ER+/HER2- advanced or metastatic breast cancer starting first- or second-line CDK4/6i with ET were enrolled in the “Impact of Endocrine Therapy and Abemaciclib on Host and Tumor Immune Cell Repertoire/Function in Advanced ER+/HER2-Breast Cancer” (NCT04352777) trial. For each patient, the same lesion was biopsied prior to treatment (T1 = baseline, pretreatment) and following four weeks of continuous abemaciclib and ET (T2 = 4 weeks post-treatment). A total of 26 pre- and post-treatment tumor biopsies from diverse sites (recurrent breast and bone, liver, and lymph node metastases) from 13 patients who had varying responses to treatment were analyzed. Following tissue dissociation, positive selection of CD45+ cells was used to enrich for tumor-infiltrating immune cells. We find that genes associated with interferon response are downregulated in T cell populations and genes associated with antigen presentation were upregulated in macrophages and dendritic cells following treatment. Raw single-cell sequencing data from the 10 patients that consented to data sharing will be made available through dbGaP.

Study phs004470

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