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• Region-specific Transcriptome Analysis of the Human Retina and Retinal Pigment Epithelium (RPE)/Choroid

  Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with regional phenotypes. Reprinted from Whitmore, S.S., Wagner, A.H., DeLuca, A.P., Drack, A.V., Stone, E.M., Tucker, B.A., Zeng, S., Braun, T.A., Mullins, R.F., Scheetz, T.E., 2014. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq. Experimental Eye Research. Used under Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported license. Additional RNA sequencing was performed on temporal, macular, nasal, inferior, and superior retina from a fifth subject and is included in this dataset. See original publication for details.

  Study phs001151

• Cancerous Adaptive Dosing Melanoma WGS Dataset

  Illumina NovaSeq 6000 30x WGS of 26 samples, each with up to 5 matched timepoints. Timepoints A,B,C,D,and E correspond to Pretreatment, Week 3, Week 6, Week 9, and Week 12 after treatment, respectively. Additional sample metadata (sample recurrence, treatment course, age, sex, comorbidities, etc.) are present in sample description.

  Dataset EGAD00001010926

• Genomic Characterization CS-MATCH-0007 Arm P

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm P is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with PTEN loss by IHC are treated with the drug GSK2636771. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002152

• RNA-seq after drug perturbation of primary lymphoma samples

  3'-end low-depth RNA sequencing data from 108 patients with chronic lymphocytic leukemia and 8 patients with lymphoma. Each primary patient sample was treated in vitro with DMSO as a control and with up to ten small-molecule inhibitors (ibrutinib, duvelisib, everolimus, trametinib, nutlin-3a, I-BET762, MK2206, selinexor, compound 26, and a combination of ibrutinib and compound 26). Sequencing was performed on the Illumina HiSeq4000. The dataset contains FASTQ files.

  Dataset EGAD50000002166

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

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

  Study EGAS50000001818

• CEITEC DAC

  A CEITEC Data Access Committee (DAC) is a body of one or more named individuals who are responsible for data release to external requesters. The members of DAC are selected members of research groups and their respective leaders. Multiple datasets may be affiliated to a single DAC. DAC continues communication with requester to understand the purpose of use, i.e. research setting the dataset is envisioned for by requester, to identify if data sharing is possible directly under current conditions for the dataset, or actions such as re-consenting is needed and desirable to accommodate the proposed research setting/data use.

  Dac EGAC50000000049

• Thirty cutaneous SCC WES tumour samples with matched normal

  Thirty cutaneous SCC WES tumour samples with matched normal include 20 samples from South et al. JID and 10 new samples. These 30 samples has been used to support the findings in the TGFb Nature Communications paper (DOI: 10.1038/ncomms12493). They are also a part of the ongoing study of cSCC genomic landscape of 40 cSCC samples in total.

  Dataset EGAD00001002253

• Genomic Characterization CS-MATCH-0007 Arm B

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing, RNA sequencing and if possible, whole-genome, methylation and miRNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH clinical trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm B is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with HER2- activating mutations are treated with Afatinib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002028

• Genomic Characterization CS-MATCH-0007 Arm Z1I

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm Z1I is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with BRCA1, BRCA2 mutations are treated with AZD1775. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002058

• Genomic Characterization CS-MATCH-0007 Arm Z1A

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm Z1A is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with NRAS mutations are treated with Binimetinib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs001973

• Genomic Characterization CS-MATCH-0007 Arm W

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm W is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with FGFR fusions, mutations, amplifications are treated with AZD4547. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including tumor tissue and whole blood.

  Study phs001948

• Genomic Characterization CS-MATCH-0007 Arm S2

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm S2 is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with GNAQ or GNA11 mutations are treated with Trametinib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002178

• Genomic Characterization CS-MATCH-0007 Arm R

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm R is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with BRAF fusions, non-V600K or non-V600E mutations, are treated with Trametinib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002029

• Genomic Characterization CS-MATCH-0007 Arm S1

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm S1 is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with NF1 mutations are treated with Trametinib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002153

• Genomic Characterization CS-MATCH-0007 Arm I

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm I is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with PIK3CA mutations (without KRAS Mutation or PTEN Loss) are treated with Taselisib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002181

• Genomic Characterization CS-MATCH-0007 Arm U

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm U is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with NF2 loss are treated with Defactinib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002179

• Genomic Characterization CS-MATCH-0007 Arm C1

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm C1 is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with MET amplification are treated with Crizotinib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002177

• Genomic Characterization CS-MATCH-0007 Arm Z1B

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm Z1B is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with CCND1, CCND2, and/or CCND3 amplifications are treated with Palbociclib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002180

• Genomic Characterization CS-MATCH-0007 Arm Q

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm Q is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with HER2 amplification are treated with Kadcyla® (ado-trastuzumab emtansine). This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including tumor tissue and whole blood.

  Study phs001926

• Genomic DNA analysis for malignant mesothelioma from the patients of Japan and USA.

  Malignant mesotheliomas (MMs) are highly aggressive adult malignancies and exposure to asbestos is the major factor involved in MM pathogenesis. It is desirable for a better understanding of the molecular pathogenesis of MM will lead to more specific and effective targeted therapies. In addition it is reported that germline mutation in a specific gene (ex. BAP1) associates familial MMs, and new candidate markers to determine a subject?s predisposition to MM and for early detection need to be identified. Analysis of genomic DNA from MM tumors and reference peripheral blood from Japan and USA are ongoing to find the common genomic characters beyond race.

  Study JGAS000108

• Exome sequencing of uterine leiomyosarcomas

  Uterine leiomyosarcomas (ULMSs) are aggressive smooth muscle tumors associated with poor clinical outcome. Despite previous cytogenetic and molecular studies, their molecular background has remained elusive. To examine somatic variation in ULMS, we performed exome sequencing on 19 tumors. Altogether 43 genes were mutated in at least two ULMSs. Most frequently mutated genes included tumor protein P53 (TP53; 6/19; 33%), alpha thalassemia/mental retardation syndrome X-linked (ATRX; 5/19; 26%), and mediator complex subunit 12 (MED12; 4/19; 21%). Unlike ATRX mutations, both TP53 and MED12 alterations have repeatedly been associated with ULMSs. All the observed ATRX alterations were either nonsense or frameshift mutations. ATRX protein levels were reliably analyzed by immunohistochemistry in altogether 44 ULMSs, and the majority of tumors (23/44; 52%) showed clearly reduced expression. Loss of ATRX expression has been associated with alternative lengthening of telomeres (ALT), and thus the telomere length was analyzed with telomere-specific fluorescence in situ hybridization. The ALT phenotype was confirmed in all ULMSs showing diminished ATRX expression. Exome data also revealed one nonsense mutation in death-domain associated protein (DAXX), another gene previously associated with ALT, and the tumor showed ALT positivity. Aberrant expression of both TP53 and ATRX were associated with poor overall survival. In conclusion, exome sequencing revealed that TP53, ATRX, and MED12 are frequently mutated in ULMSs. ALT phenotype was commonly seen in tumors, indicating that ATR inhibitors, which were recently suggested as possible new drugs for ATRX-deficient tumors, could provide a potential novel therapeutic option for ULMS.

  Study EGAS00001001612

• Nala GSI GSAv3 PGx Study

  Background: Microarrays are a well-established and widely adopted technology capable of interrogating hundreds of thousands of loci across the human genome. Combined with imputation to cover common variants not included in the chip design, they offer a cost-effective solution for large-scale genetic studies. Beyond research applications, this technology can be applied for testing pharmacogenomics, nutrigenetics, and complex disease risk prediction. However, establishing clinical reporting workflows requires a thorough evaluation of the assay's performance, which is achieved through validation studies. In this study, we performed pre-clinical validation of a genetic testing workflow based on the Illumina Global Screening Array for 25 pharmacogenomic-related genes. Methods: To evaluate the accuracy of our workflow, we conducted multiple pre-clinical validation studies. Here, we present the results of accuracy and precision assessments, involving a total of 73 cell lines. These assessments encompass reference materials from the Genome-In-A-Bottle (GIAB), the Genetic Testing Reference Material Coordination Program (GeT-RM) projects, as well as additional samples from the 1000 Genomes project (1KGP). We conducted an accuracy assessment of genotype calls for target loci in each indication against established truth sets. Results: In our per-sample analysis, we observed a mean analytical sensitivity of 99.39% and specificity 99.98%. We further assessed the accuracy of star-allele calls by relying on established diplotypes in the GeT-RM catalogue or calls made based on 1KGP genotyping. On average, we detected a diplotype concordance rate of 96.47% across 14 pharmacogenomic-related genes with star allele-calls. Lastly, we evaluated the reproducibility of our findings across replicates and observed 99.48% diplotype and 100 % phenotype inter-run concordance. Conclusion: Our comprehensive validation study demonstrates the robustness and reliability of the developed workflow, supporting its readiness for further development for applied testing.

  Study EGAS00001007710

• Risk alleles of membranous nephropathy and recurrence of the disease on the grafted kidney

  Samples are from patients enrolled in an international multicentric study aimed to define the genetic determinants of recurrence of membranous nephropathy in the kidney graft. They include 248 samples from patients with MN including 105 patients who received a graft, their 105 graft donors, and 192 controls all of Caucasian origin. Files from targeted-capture of HLA and PLA2R loci are available as fastq files.

  Dataset EGAD00001007831

• FinHer Breast Cancer Study

  The purpose of this study is to sequence 500 known cancer genes in 960 newly diagnosed high risk breast cancer patients treated with current standard of care therapies and trastuzumab, for somatic alteration and copy number changes. We will be using next gen sequencing technology to determine the prognostic relevance of these somatic genetic alterations and of teh low frequency events to determine if they are associated with trastuzumab benefit or HER2 positive breast cancer, i.e. treatment interaction. The samples will be analysed adn correlated with clinical variables including outcome.

  Dataset EGAD00001000871

• Gabriella Miller Kids First Pediatric Research Program in Pediatric T-Cell Acute Lymphoblastic Leukemia

  The outcome for patients with relapsed T-ALL is dismal with 3-year event free survival of AALL0434 was a Children's Oncology Group-initiated phase 3 randomized clinical trial comparing Capizzi-style escalating methotrexate plus pegaspargase (CMTX) vs. high dose methotrexate (HDMTX), with/without six 5-day courses of nelarabine. Survival on this study was superior to any prior trial for de novo T-ALL, changing the standard of care. Yet, a substantial minority (~15%) of patients had relapsed or refractory (r/r) disease. Through the TARGET initiative, RNA sequencing (RNA-Seq), DNA copy number analysis, and whole-exome sequencing (WES) were performed on 264 T-ALL patients treated on AALL0434, demonstrating recurrent alterations could be grouped into 10 different potentially targetable functional pathways. This analysis was not powered to examine associations between genetic lesions with outcome, because too few patients with r/r disease were included. This project is dedicated to testing the hypothesis that comprehensive genomic profiling of the entire AALL0434 cohort will identify recurrent genetic alterations that can be segregated into biologically relevant deregulated pathways that can be combined with MRD to identify patients at risk for poor outcomes before they relapse and provide rationale for treatment with alternative therapies. In addition, a number of small recent studies demonstrated that many of the biologically relevant alterations in T-ALL occur in non-coding regions of the genome, but no large studies have performed whole genome sequencing (WGS) in T-ALL. This project also tests the hypothesis that WGS of a large cohort of patients with T-ALL will identify novel lesions in coding and non-coding regions that will be highly impactful in the understanding of T-ALL pathogenesis.These hypotheses are tested by performing comprehensive genomic profiling (WGS, WES, RNA-Seq, and copy number analysis) of the entire AALL0434 cohort with available samples with the following specific aims: (1) identify recurrent genetic alterations that predict poor outcome in T-ALL; (2) identify novel alterations, including non-coding alterations in T-ALL; and (3) identify germline genetic variants that predispose to T-ALL and to increased toxicity to chemotherapy.

  Study phs002276