Frequently Asked Questions
OCG is currently building an FAQ based on the needs of our users. We will be updating questions on this site continually, so visitors should check back soon for new FAQs. If you cannot find what you are looking for here, please do not hesitate to contact us
Tumor mutational frequency is affected by a number of factors including cancer type, tissue status, and patient age. Because the open-access masked somatic MAF data are heavily filtered to remove potential germline variants (for more information see: https://docs.gdc.cancer.gov/Data/File_Formats/MAF_Format/), there are instances where these files may not contain low frequency somatic variants. If omission of true-positive somatic mutations is a concern, we recommend accessing controlled-access MAFs through GDC, which requires user certification through dbGaP. copy number variation and structural rearrangement data files are also generated and may be useful to the end user.
Two examples of GDC open-access masked somatic MAF files with no called variants are:
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Users can identify models with research somatic and/or clinical variants in the gene(s) of interest by using the “Search by Gene” search box in the filter panel on the left-hand side of the HCMI Searchable Catalog. As gene(s) of interest are selected, the list of models containing any variants in the gene(s) of interest will appear within the main viewing table. The example below shows the list of models that contain research somatic and/or clinical variants in the BRAF gene. Additionally, the “Most Frequently Mutated Genes” bar graph at the top of the Catalog can be used to identify models with research somatic and/or clinical variants in the gene(s) of interest by clicking on any data column within the graph.
Note: The open-access masked somatic MAF data shown in the Catalog is generated at NCI’s Genomic Data Commons (GDC). These data are highly processed to remove low frequency somatic variants and potential germline variants (for more information see: https://docs.gdc.cancer.gov/Data/File_Formats/MAF_Format/). If omission of true-positive somatic mutations is a concern, we recommend accessing controlled-access MAFs through GDC, which requires user certification through dbGaP. The clinical variant data provided is reported from the Case Report Forms (CRF).
As part of NCI's Genomic Data Commons’ (GDC) harmonization process, potential germline mutations are filtered from the variants identified by DNA sequencing of the model and normal tissues. These highly-filtered lists of somatic mutations without the germline variants are called “masked somatic mutations”, and they are available to users as open-access “masked somatic MAF” files for each model. Once cases are released at the GDC, the available masked somatic MAF model data are shown as “Research Somatic Variants” on the HCMI Searchable Catalog. Catalog users may search the available models for gene mutations of interest.
Clinical Variants contain the cancer type-specific prognostic or predictive variants identified by clinical sequencing and/or histopathological staining as reported in the Case Report Forms. The cancer type-specific clinical variants represented in the HCMI Case Report Forms incorporates input from teams of international clinical collaborators.
The cancer types that are not highly represented in the HCMI models are considered “rare” by HCMI, however, they may not be considered “rare” based on their representation among cancer incidence rates. The “Rare Cancer CRFs” are being used to capture clinical data for these cancer types: Bladder Cancer, Chordoma, Epithelioid Sarcoma, Extrahepatic Cholangiocarcinoma, Gallbladder Cancer, Spindle Cell Sarcoma, Small Intestine Cancer, and Thyroid Cancer.
HCMI Searchable Catalog is a continuously updated resource for querying the available next-generation models developed by HCMI. Within the Catalog, users can search by patient demographics, tumor, and model elements including age at diagnosis, sex, treatment information, clinical tumor diagnosis, primary site, clinical stage, and type of model (e.g. 3D-organoid, 2D-conditionally reprogrammed cells), etc. For additional assistance in navigating the Searchable Catalog, please see the “HCMI Searchable Catalog User Guide”.
- Tuveson D, Clevers H. Cancer modeling meets human organoid technology. Science. 2019;364(6444):952-955. doi:10.1126/science.aaw6985 (PMID: 31171691)
- Zou Y, Palte MJ, Deik AA, et al. A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis. Nat Commun. 2019;10(1):1617. Published 2019 Apr 8. doi:10.1038/s41467-019-09277-9 (PMID: 30962421)
- Chan EM, Shibue T, McFarland JM, et al. WRN helicase is a synthetic lethal target in microsatellite unstable cancers. Nature. 2019;568(7753):551-556. doi:10.1038/s41586-019-1102-x (PMID: 30971823)
- Tiriac H, Plenker D, Baker LA, Tuveson DA. Organoid models for translational pancreatic cancer research. Curr Opin Genet Dev. 2019; 54:7-11. doi:10.1016/j.gde.2019.02.003 (PMID: 30844513)
- Neal JT, Li X, Zhu J, et al. Organoid Modeling of the Tumor Immune Microenvironment. Cell. 2018;175(7):1972-1988.e16. doi: 10.1016/j.cell.2018.11.021(PMID: 30550791)
- Tiriac H, Belleau P, Engle DD, et al. Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer. Cancer Discov. 2018;8(9):1112-1129. doi:10.1158/2159-8290.CD-18-0349 (PMID: 29853643)
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- Buczacki SJA, Popova S, Biggs E, et al. Itraconazole targets cell cycle heterogeneity in colorectal cancer. J Exp Med. 2018;215(7):1891-1912. doi:10.1084/jem.20171385 (PMID: 29853607)
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- Boj SF, Hwang CI, Baker LA, et al. Organoid models of human and mouse ductal pancreatic cancer. Cell. 2015 Jan 15;160(1-2):324-38. (PMID: 25557080)
- Baker LA, Tiriac H, Clevers H, Tuveson DA. Modeling pancreatic cancer with organoids. Trends in Cancer. 2016 Apr;2(4):176-190. (PMID: 27135056)
Please see HCMI publication guidelines for guidance on how to acknowledge HCMI. The initiative members plan to publish a joint comprehensive manuscript when the number of models released reaches a critical number. Therefore, the consortium requests that investigators do not publish a manuscript using a large cohort of HCMI models and data before the paper is published. Use and publication of up to five models is acceptable.
Models' case-associated clinical, biospecimen, and molecular characterization data are available at NCI’s Genomic Data Commons (GDC). New data is released at the GDC when it becomes available. The GDC uses an email listserv to provide information on data releases. Information about accessing controlled-access data, visit: https://ocg.cancer.gov/programs/hcmi/accessing-hcmi-data.
A model's case-associated data include the data from the derived model, originating tumor tissue and normal tissue. Quality checked clinical, biospecimen, and molecular characterization data are available for HCMI models at NCI’s Genomic Data Commons (GDC). While the consortium aims to provide comprehensive data, availability of models' case-associated information may differ among cancer model development centers.
Available HCMI models can be found on HCMI Search Catalog page. Individual model pages contain a subset of model associated data, and a link to available associated molecular characterization and clinical data at NCI’s Genomic Data Commons (GDC). The link to the 3rd party HCMI Model Distributor is also available. The HCMI Searchable Catalog is a dynamic resource and is updated as model-associated data become available.
See the HCMI Searchable Catalog User Guide for guidance on navigating the Searchable Catalog.
- Informed Consent Template for Tissue Accrual to Enable Model Development and Distribution
- Case Report Forms for clinical data collection
- Protocols for model expansion
No, all of the HCMI next-generation cancer models are derived from primary patient tissues.
The initiative members plan to publish a joint comprehensive manuscript when the number of models released reaches a critical number. Therefore, the consortium requests that investigators do not publish a manuscript using a large cohort of HCMI models and data before the paper is published. Use and publication of up to five models is acceptable.