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• Light at Night and Prostate Cancer in the Health Professionals Follow-Up Study

  The Health Professionals Follow-Up Study (HPFS) is a prospective cohort study of men designed to evaluate hypotheses about men's health related to diet and lifestyle to the incidence of serious illnesses, such as cancer, heart disease, and other vascular diseases. It consisted of 51,529 U.S. male health professionals who were 40-75 years old at baseline in 1986 and completed a mailed six-page baseline questionnaire. Information on age, height, weight, ancestry, medications, disease history, physical activity, lifestyle factors, and diet were gathered, with follow-up questionnaires sent biennially to update information and record health outcomes with every four years to update their diet. Light at Night and Prostate Cancer project uses HPFS participants to conduct research assessing the impact of light at night on prostate cancer incidence, with follow-up from baseline in 1986 to 2016. Average annual outdoor light at night (exposure) was derived from satellite imagery data from the US Defense Meteorological Satellite Program's Operational Linescan System (maintained by the National Oceanic and Atmospheric Administration's Earth Observation Group). Prostate cancer cases (outcome) were self-reported by study participants, and then confirmed by the HPFS team through medical record and pathology report review. The data for this project are arranged in a long format, meaning that there are multiple rows for each subject ID. The various rows correspond to different questionnaire periods. Because the exposure in this dataset, light at night, and several important covariates are time-varying variables, the format of this dataset captures the variation in exposure status by questionnaire period. The outcome variables are incidence of prostate cancer, including incidence of prostate cancer clinical subtypes, such as advanced, aggressive, high- and low-grade prostate cancer. For the published study, please see Chowdhury-Paulino et al.'s 2023 publication in Cancer Epidemiology Biomarkers and Prevention entitled, “Association between Outdoor Light at Night and Prostate Cancer in the Health Professionals Follow-up Study.” (PMID: 37462694).

  Study phs003538

• Precision High Intensity Training Through Epigenetics (PHITE)

  Exercising regularly promotes health, but these benefits are complicated by acute inflammation induced by exercise. A potential source of exercise-induced inflammation is cell-free DNA (cfDNA), yet the cellular origins, molecular causes, and immune system interactions of exercise-induced cfDNA are unclear. To study these, 10 healthy individuals were randomized to a 12-week exercise program of either high-intensity tactical training (HITT) or traditional moderate-intensity training (TRAD). Blood plasma was collected pre- and post exercise at weeks 0 and 12 and after 4 week of detraining upon program completion. Whole-genome enzymatic methylation sequencing (EM-seq) with cell-type proportion deconvolution was applied to cfDNA obtained from the 50 plasma samples and paired to concentration measurements for 90 circulating cytokines. Acute exercise increased the release of cfDNA from neutrophils, dendritic cells (DCs), and macrophages proportional to exercise intensity (HITT > TRAD). Exercise training reduced cfDNA released in HITT participants but not TRAD and from DCs and macrophages but not neutrophils. For most participants, training lowered mitochondrial cfDNA at rest, even after detraining. Using a sequencing analysis approach we developed, we concluded that rapid extracellular traps (ETosis) was the likely source of cfDNA, demonstrated by enrichment of nuclear DNA. Further, several cytokines were induced by acute exercise, such as IL-6, IL-10, and IL-16, and training attenuated the induction of only IL-6 and IL-17F. Cytokine levels were not associated with cfDNA induction, suggesting that these cytokines are not the main cause of exercise-induced cfDNA. Overall, exercise intensity and training modulated cfDNA release and cytokine responses, contributing to the anti-inflammatory effects of regular exercise. One additional subject was also used in the methyl-seq data as a control for comparing bisulfite-sequencing to enzymatic methyl sequencing. DNA methylation for MPO gene was found to be significantly different as well, in line with interpretation that neutrophils are primarily undergoing ETosis.

  Study phs003873

• McGill Epigenomics Mapping Centre

  The McGill Epigenomics Mapping Centre (EMC) and Data Coordination Centre (EDCC) were established in 2012 at the McGill University and Genome Quebec Innovation Centre (Montreal, Canada) to support large-scale human epigenome mapping for a broad spectrum of cell types and diseases. Previous epigenetic studies have provided profiles of specific chromatin marks in relation to basic biological processes, and future studies of molecular mechanisms must build upon these proofs-of-concept by integrating sequence-based variation with multiple levels of epigenetic and transcriptional regulation across the genome of human tissues and animal disease models. This project leverages the high-throughput sequencing infrastructure and expertise in genomics and transcriptomics at the McGill Innovation Centre to carry out this research. Controlled access to the data by collaborators and the greater scientific community is gained via a portal, which takes advantage of Compute Canada high-performance computing cluster resources to manage the large volume of data associated from the generation of reference epigenome maps. McGill University is one of two Canadian mapping and data coordination centres, the other based at the Michael Smith Genome Sciences Centre in Vancouver, British Columbia. The generation of comprehensive epigenome maps at McGill University is part of a larger international effort that is coordinated by the International Human Epigenome Consortium (IHEC), whose overall long-term objective is to determine the extent to which the epigenome shapes human populations over generations and in response to the environment. This project is funded under the Canadian Epigenetics, Environment, and Health Research Consortium (CEEHRC) by the Canadian Institutes of Health Research and by Genome Quebec, with additional support from Genome Canada. The computing and networking infrastructure, and part of the software development, are provided by Compute Canada and CANARIE.

  Study EGAS00001000995

• Same-day genomic and epigenomic diagnosis of brain tumors using realtime nanopore sequencing

  Molecular classification of cancer has entered clinical routine to inform diagnosis, prognosis and treatment decisions. At the same time, new tumor entities have been identified that cannot be defined histologically. For central nervous systems tumors, the current World Health Organization classification explicitly demands molecular testing, e.g. for 1p/19q- codeletion or IDH mutations, to make an integrated histomolecular diagnosis. However, a plethora of sophisticated technologies is currently needed to assess different genomic and epigenomic alterations and turnaround times are in the range of weeks, which makes standardized and widespread implementation difficult and hinders timely decision making. Here, we explored the potential of a pocket-size nanopore sequencing device for multimodal and rapid molecular diagnostics of cancer. Low-pass whole genome sequencing was used to simultaneously generate copy number (CN) and methylation profiles from native tumor DNA in the same sequencing run. Single nucleotide variants in IDH1, IDH2, TP53, H3F3A and the TERT promoter region were identified using deep amplicon sequencing. Nanopore sequencing yielded ~0.1X genome coverage within six hours and resulting CN and epigenetic profiles correlated well with matched microarray data. Diagnostically relevant alterations, such as 1p/19q codeletion, and focal amplifications could be recapitulated. Using ad hoc random forests, we could perform supervised pan-cancer classification to distinguish gliomas, medulloblastomas and brain metastases of different primary sites. Single nucleotide variants in IDH1, IDH2 and H3F3A were identified using deep amplicon sequencing within minutes of sequencing. Detection of TP53 and TERT promoter mutations shows that sequencing of entire genes and GC-rich regions is feasible. Nanopore sequencing allows same-day detection of structural variants, point mutations and methylation profiling using a single device with negligible capital cost. It outperforms hybridization-based and current sequencing technologies with respect to time-to diagnosis and required laboratory equipment and expertise, aiming to make precision medicine possible for every cancer patient, even in resource restricted settings.

  Study EGAS00001002213

• Somatic copy number alteration and fragmentation analysis in circulating tumor DNA for cancer screening and treatment monitoring in colorectal cancer patients

  Background: Analysis of circulating free DNA (cfDNA) is a promising tool for personalized management of colorectal cancer (CRC) patients. Untargeted cfDNA analysis using whole-genome sequencing (WGS) does not need a priori knowledge of the patient´s mutation profile. Methods: Here we established LIquid biopsy Fragmentation, Epigenetic signature and Copy Number Alteration analysis (LIFE-CNA) using WGS with ~6x coverage for detection of circulating tumor DNA (ctDNA) in CRC patients as a marker for CRC detection and monitoring. Results: We describe the analytical validity and a clinical proof-of-concept of LIFE-CNA using a total of 259 plasma samples collected from 50 patients with stage I-IV CRC and 61 healthy controls. To reliably distinguish CRC patients from healthy controls, we determined cutoffs for the detection of ctDNA based on global and regional cfDNA fragmentation patterns, transcriptionally active chromatin sites, and SCNAs. We further combined global and regional fragmentation pattern into a machine learning classifier to accurately predict ctDNA for cancer detection. By following individual patients throughout their course of disease, we show that LIFE-CNA enables the reliable prediction of response or resistance to treatment up to 3.5 months before commonly used CEA. Conclusion: In summary, we developed and validated a sensitive and cost-effective method for untargeted ctDNA detection at diagnosis as well as for treatment monitoring of all CRC patients based on genetic as well as non-genetic tumor-specific cfDNA features. Thus, once sensitivity and specificity have been externally validated, LIFE-CNA has the potential to be implemented into clinical practice. To the best of our knowledge, this is the first study to consider multiple genetic and non-genetic cfDNA features in combination with ML classifiers and to evaluate their potential in both cancer detection and treatment monitoring.

  Study EGAS00001006490

• A Dormant TIL Phenotype Defines Non-Small Cell Lung Carcinomas Sensitive to Immune Checkpoint Blockers

  The biological determinants of sensitivity and resistance to immune checkpoint inhibitors are not completely understood. To elucidate the role of intratumoral T-cells and its association with the tumor genomic landscape, we perform paired whole exome DNA sequencing and multiplexed quantitative immunofluorescence (QIF) in pre-treatment samples from non-small cell lung carcinoma patients treated with PD-1 axis blockers. QIF was used to simultaneously measure the level of CD3+ tumor infiltrating lymphocytes (TILs), in situ T-cell proliferation (Ki-67 in CD3) and effector capacity (Granzyme-B in CD3). Whole exome sequencing reported in the number/type of mutations and predicted class I and class II mutant neoantigens.

  Study phs001618

• A comprehensive proteogenomic pipeline for neoantigen discovery to advance personalized cancer immunotherapy

  The accurate identification and prioritization of antigenic peptides is crucial for the development of personalized cancer immunotherapies. Publicly available pipelines to predict clinical neoantigens do not allow direct integration of mass spectrometry immunopeptidomics data, which can uncover antigenic peptides derived from various canonical and non-canonical sources. To address this, we present an end-to-end clinical proteogenomic pipeline, called NeoDisc, that combines state-of-the-art publicly available and in-house software for immunopeptidomics, genomics and transcriptomics with in-silico tools for the identification, prediction, and prioritization of tumor-specific and immunogenic antigens from multiple sources, including neoantigens, viral antigens and high-confidence tumor-specific antigens.

  Study EGAS50000000228

• The mutational landscape of skin tumours in CYLD cutaneous syndrome determined

  Patients with germline mutations in CYLD can develop hundreds of benign skin tumours called cylindromas. The development of multiple tumours within a single patient at sun-protected and sun-exposed sites, varying tumour histological patterns and grades of malignancy allow for the testing of several genetic hypothesis in relation to cutaneous carcinogenesis. By adopting the unprecedented approach of whole genome sequencing of multiple benign skin tumours within individuals in multigenerational families, we set out to study the impact of mutational diversity on models such as multistep carcinogenesis as well as non-sequential carcinogenesis. Using non-negative matrix factorisation (NMF) to discover mutational signatures, we found distinct mutational signatures in identical benign tumours (N=2 patients; n=11 tumours) at sun exposed and sun protected skin tumours within a mother and her daughter. We found recurrent mutations in epigenetic modifying genes in CCS tumours which are known to have an oncogenic dependency on Wnt signalling. We also demonstrate that cutaneous tumours that metastasize to the lung carry a a UV signature, supporting the origin from the skin. Distinct malignant tumours, such as BCC and malignant spiradenocarcinoma carried unique driver mutations. These findings add new dimensions to the existing paradigms of UV-induced skin cancer and highlight the utility of studying rare disease to gain novel insights into genetic mechanisms of tumour formation.

  Dataset EGAD00001004573

• Elevated somatic mutation burdens in normal human cells due to defective DNA polymerases

  Mutation accumulation over time in normal somatic cells contributes to cancer development and is proposed as a cause of ageing. DNA polymerases POLE and POLD1 replicate DNA with high fidelity during normal cell divisions. However, in some cancers defective proofreading due to acquired mutations in the exonuclease domains of POLE or POLD1 causes markedly elevated somatic mutation burdens with distinctive mutational signatures. POLE and POLD1 exonuclease domain mutations also cause familial cancer predisposition when inherited through the germline. Here, we sequenced normal tissue DNA from individuals with germline POLE or POLD1 exonuclease domain mutations. Increased mutation burdens with characteristic mutational signatures were found to varying extents in all normal adult somatic cell types examined, during early embryogenesis and in sperm. Mutation burdens were further markedly elevated in neoplasms from these individuals. Thus human physiology is able to tolerate ubiquitously elevated mutation burdens. Indeed, with the exception of early onset cancer, individuals with germline POLE and POLD1 exonuclease domain mutations are not reported to show abnormal phenotypic features, including those of premature ageing. The results, therefore, do not support a simple model in which all features of ageing are attributable to widespread cell malfunction directly resulting from somatic mutation burdens accrued during life.

  Dataset EGAD00001006212

• EGA submission account terms

  Submission account terms Each EGA submission account has a dedicated submission box. To ensure continued service to all submitters EGA submission boxes should not exceed 8Tb in size, and cannot exceed 12Tb. Those that are near to or exceeding this value will be monitored on a weekly basis by the helpdesk team and the submitter will be contacted and guidance provided accordingly on completing their metadata registration. You will be able to register your metadata associated with the files in your submission account via EGA Submitter Portal, Webin or the EGA REST API. EGA also requests that metadata is submitted within 60 days of upload data to a submission box. When we detect files that are over 60 days old in a submission box we will notify the submitter requesting that metadata be submitted or the files removed from the submission box. It is important to note that data is not archived at the EGA until the metadata describing the files has been associated and the archival process has completed. It is only when associated metadata has been submitted that the archival process into EGA is fully triggered. EGA removes files from the submission box once they have been successfully archived, so no action is required by a submitter to remove successfully archived files. Files over 90 days old will be deleted from the submission box unless EGA Helpdesk has been contacted and confirmed an exemption with the submitter.

  Documentation submission/terms

• Center for Craniofacial and Dental Genetics (CCDG): Genetics of Orofacial Clefts and Related Phenotypes

  The purpose of this study is to investigate the genetics of orofacial clefts (OFCs) in a large study population, and importantly, to incorporate subclinical phenotypic features into these studies. Orofacial clefts (OFCs) comprise a significant fraction of human birth defects (about 1/700 live births (Rahimov et al. 2012) and represent a major public health challenge, as individuals with these anomalies require surgical, nutritional, dental, speech, medical and behavioral interventions, thus imposing a substantial economic and personal burden (Berk and Marazita 2002*). The most common forms include OFCs of the lip alone (CL, Figure 1A), CL plus cleft palate (CL+CP, Figure 1B) or of the palate only (CP, Figure 1C). Individuals born with OFC may have their first surgical repair at age 3 months, but this initial surgery is just the beginning of a lifetime of health burdens. An individual born with an OFC has a hospital use rate increased for most ages (up to 233% increase for children ages 0-10 years and 16% for middle aged adults (Wehby et al. 2012). Healthcare costs for children with OFCs are estimated to be 800% greater compared with their unaffected peers (Boulet et al. 2009). Data from Denmark show that people born with CL with or without CP (CL/P) have an increased mortality up to age 55, which may be attributed to an increased risk of suicide and/or certain cancers (Christensen et al. 2004). The focus of most OFC genetic research has been CL and/or CP. Furthermore, the majority of OFC, i.e. about 70% of CL/P and 50% of CP is considered "nonsyndromic" (Jones 1988), i.e. isolated anomalies with no other apparent cognitive or structural abnormalities. Figure 1 Sample OFC Types A: Bilateral Cleft Lip; B:Cleft Lip plus Cleft Palate; C:Cleft Palate Alone The factors leading to the majority of nonsyndromic OFCs are still unclear, particularly at an individual family level. As is true for many complex traits, substantial progress in gene identification has occurred in the OFC field in the last two years (Dixon et al. 2011; Marazita 2012). Genome Wide Association Studies (GWAS) and sequencing studies to date by our research team and others have focused on genetic risk factors for overt CL/P and CPO-and have been very successful. A major finding from this work is that OFCs exhibit significant genetic heterogeneity, i.e., multiple genetic regions have been implicated (Beaty et al. 2010; Ludwig et al. 2012). Thus, approaches are needed to understand this genetic heterogeneity. Are there GxG interactions at work? Are there subsets of families, each due to a different gene? Our research group has shown that a promising approach to dissect the etiology of OFC is to focus on subclinical phenotypic features within entire cleft families (not just in affected cases, but also in their non-cleft relatives). These subtle features are believed to represent mild manifestations of the same underlying genetic susceptibility responsible for OFCs; as such, their inclusion in case-control and family-based genetic studies can help to clarify and refine the relationship between genotype and phenotype. The study population comprises a large number of families and individuals (~12,000 individuals) from multiple populations worldwide (Caucasians from the US and Europe, Asians from China and the Philippines, Mixed Native American/Caucasians from South America, and Africans from Nigeria and Ethiopia). There are cases, case families (nuclear families and extended kindreds), as well as controls with no history of OFC nor other developmental defects. *Berk NW, Marazita ML (2002) Costs of Cleft lip and Palate: Personal and Societal Implications. In: Wyszynski DF (ed) Cleft Lip and Palate: From Origin to Treatment. Oxford University Press, Inc., New York, pp 458-467.

  Study phs000774

• Single-cell genotype-to-phenotype mapping via co-capture of DNA mutations and mRNA transcripts

  We developed single-cell Genotype-to-Phenotype sequencing (scG2P) for high-throughput, highly-multiplexed, single-cell joint capture of recurrently mutated genomic regions and mRNA phenotypic markers in cells or nuclei isolated from solid tissues. We applied scG2P to aged esophagus samples from five individuals with high alcohol and tobacco exposure.

  Dac EGAC50000000833

• Enhancer plasticity in endometrial tumorigenesis demarcates non-coding driver mutations and alterations in 3D genome organization to boost oncogene expression

  Understand whether and how ERα can drive endometrial tumorigenesis. Study the mechanisms that lead to endometrial tumor progression and metastasis formation.

  Study EGAS00001007240

• Whole genome sequencing identified biomarker of response to PD1 blockade in Natural-killer/T-cell lymphoma

  WGS data of 13 and TCS data of 8 NKTCL patients. Significant association of PD-L1 rearrangements with objective response to anti-PD1 (pembrolizumab).

  Study EGAS00001002420

• Patient-derived conditionally reprogrammed cells (CRCs) were established and characterized to assess their biological properties and to apply these to test the efficacies of drugs.

  RNA seq data was used for the characterization and profiling of the created patient-derived cells and in vivo tissue.

  Study EGAS00001001702

• Molecular Phenotyping to Accelerate Genomic Epidemiology (MolPAGE)

  MolPAGE is an integrated EU project that aims to develop methods and tools for discovery of biomarkers associated with diabetes (see www.ocdem.ox.ac.uk for MolOBB and www.twinsuk.ac.uk for MolTWIN).

  Study EGAS00000000102

• RNA dataset of ALK study

  Here we sequenced biopsies from a patient with ALK-positive NSCLC progressing on first-line lorlatinib. This dataset contains one mRNA-seq and one Total-RNAseq. This aims to investigate the impact of the K1150dup mutation on lorlatinib progression and to explore potential therapeutic strategies to overcome resistance.

  Dataset EGAD50000002553

• COLONOMICS small RNA sequencing

  This dataset consists of SOLiD small RNA-seq of 250 colorectal samples: 100 tumor tissue samples, 100 normal tissue samples (adjacent to tumor sites) and 50 matched control samples of healthy individuals. CSfasta and qual files converted to single fastq files prior to uploading.

  Dataset EGAD00001004827

• 2017_ AML prospective data analysis result

  This data is belong to 2017 AML prospective data which is aligned to human reference(human_g1k_v37.fasta). There are 10 paired tumor/normal samples from SNUH. All samples has passed QC and recalibration steps while aligning to reference.

  Dataset EGAD00001003598

• 2017_ AML WGS analysis result

  This data is belong to 2017 AML genome data which is aligned to human reference(human_g1k_v37.fasta). There are 10 paired tumor/normal samples from SNUH. All samples has passed QC and recalibration steps while aligning to reference.

  Dataset EGAD00001003599

• RNA sequencing of control OM cells exposed to traffic-related air pollutants

  Total RNA sequencing of olfactory mucosa (OM) cells derived from cognitively healthy individuals exposed to traffic-related ultrafine particles (UFPs) for 24h and 72h in submerged cultures. The UFPs used for exposures were: A0, A20 and Euro6. Exposures were compared to the corresponding blank samples.

  Dataset EGAD00001011317

• genome-wide cfDNA methylation analysis

  To characterise cfDNA methylome in metastatic prostate cancer

  Study EGAS00001003958

• Genetic Factors associated with Conversion from Active Surveillance to Treatment for Prostate Cancer

  This is a genome-wide association study (GWAS) of conversion from active surveillance (AS) for prostate cancer (PC) to treatment. AS is the monitoring with screening tests and/or biopsies over time of men usually with low-risk, early-stage PC to avoid harmful side effects of PC treatment. "Conversion" refers to patients who withdraw from AS (switch to active treatment) due to changes in their cancer development, anxiety about delayed treatment, or other reasons. Patients who converted because of anxiety alone were censored in the GWAS analysis. The overall goal of this study is to develop an easily measurable, germline-based panel of genetic variants to aid in selecting PC patients appropriate for AS and/or the intensity of monitoring. In total, 6,324 PC patients from 28 collaborating institutions are included in this study. Patients are those with PC who are either on AS or who have previously converted from AS to treatment. In this study, 70% of all subjects were diagnosed with very low-risk, low-risk, or low-volume intermediate-risk PC (Kryvenko and Epstein, 2016; PMID: 26709152) and have been enrolled in an AS program. DNA was extracted from blood, saliva, or formalin-fixed, paraffin-embedded (FFPE) tissue collected from the study subjects at the participating sites. Genotyping, quality control processes, and imputation were performed at the Center for Inherited Disease Research (CIDR) at Johns Hopkins University. CIDR used the Illumina Infinium Multi-Ethnic Global Array (MEGA) version 1, which included genome-wide tag SNPs and 10,000 SNPs selected with custom content. Quality control and assurance (QC/QA) checks on genotyped data involved four domains: sample-level checks, batch effects, SNP-level checks, and preliminary association tests. Samples and SNPs passing the QC/QA checks were imputed to appropriate reference panels (HRC r1.1 for patients of European ancestry) using the Michigan Imputation Server (PMID: 27571263). Unmeasured genetic variants were imputed using the Trans-Omics for Precision Medicine (TOPMed) Imputation Server, with 97,256 reference samples and 308,107,085 SNPs. Variants with imputation quality (INFO) score < 0.3 were excluded, leaving a total of 22,691,641 SNPs successfully imputed. After QC steps, a total of 5,936 samples genotyped at CIDR remained for inclusion in the GWAS.

  Study phs002056

• International Consortium to Identify Genes and Interactions Controlling Oral Clefts

  Oral clefts represent the most common group of craniofacial birth defects in humans, and include cleft lip with or without cleft palate (CL/P) and cleft palate (CP). Oral clefts have a complex and heterogeneous etiology, with strong evidence for both genetic and environmental causal factors. Candidate gene studies and genome wide linkage studies have yielded compelling but inconsistent evidence that multiple genes control risk, and several studies have shown evidence for interaction between genes and environmental exposures, especially maternal smoking and nutrient intake. This consortium pulls together a very large collection of cases and their parents from multiple populations, and offers a unique opportunity to expand the search for genes controlling risk to the genome wide level. The specific aims are: To conduct a genome wide analysis on 2000+ case-parent trios ascertained through a case with isolated, non-syndromic CL/P or CP to test for linkage and disequilibrium. Initial analysis will consist of individual tests for gene effects while simultaneously testing for GxE interaction with common maternal exposures including vitamin supplementation, cigarette smoking and alcohol consumption (which have all been implicated as environmental risk factors for oral clefts). To use haplotypes in tests for GxE interaction incorporating population specific estimates. Since haplotype frequencies vary among populations, trios will be assigned haplotypes in a stratified estimation and then a pooled test statistic will be constructed. To test for interaction between SNPs in different genes showing evidence of influencing risk in a test for GxG interaction. To test for interaction between genes and maternal biomarkers using trios from Utah where measures of plasma folate, vitamin B-6, homocysteine and zinc in mothers are available. This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org), which was developed through the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to oral clefts through large-scale genome-wide association studies of well-characterized cases and their parents from multiple populations. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). The study was supported by the National Institute of Dental and Craniofacial Research (NIDCR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.

  Study phs000094

• Drug screening of patient-derived organoids from colorectal peritoneal metastases

  Colorectal cancer (CRC) patients with peritoneal metastases (CRPM) have limited treatment options and the lowest CRC survival rates. We trialed the possibility of organoid directed precision treatment for CRPM patients. CRPM organoids (peritonoids) isolated from patients underwent next-generation sequencing and medium-throughput drug panel testing ex vivo to identify specific drug sensitivities for each patient. We measured the utility of such a service including: success of peritonoid generation, time to cultivate peritonoids, reproducibility of the medium-throughput drug testing, and documented changes to clinical therapy as a result of the testing. Peritonoids were successfully generated and validated from 68% (19/28) of patients undergoing standard care. Genomic and drug profiling was completed within 8 weeks and a formal report ranking drug sensitivities was provided to the medical oncology team upon failure of standard care treatment. This resulted in a treatment change for 2 patients, one of whom had a partial response despite previously progressing on multiple rounds of standard care chemotherapy. The barrier to implementing this technology in Australia is the need for drug access and funding for off-label indications. In conclusion, our approach is feasible, reproducible and can guide novel therapeutic choices in this poor prognosis cohort, where new treatment options are urgently needed. This platform is relevant to many solid organ malignancies.

  Study phs002023