A first-generation pediatric cancer dependency map
Open accessAbstract
Exciting therapeutic targets are emerging from CRISPR-based screens of high mutational-burden adult cancers. A key question, however, is whether functional genomic approaches will yield new targets in pediatric cancers, known for remarkably few mutations, which often encode proteins considered challenging drug targets. To address this, we created a first-generation pediatric cancer dependency map representing 13 pediatric solid and brain tumor types. Eighty-two pediatric cancer cell lines were subjected to genome-scale CRISPR-Cas9 loss-of-function screening to identify genes required for cell survival. In contrast to the finding that pediatric cancers harbor fewer somatic mutations, we found a similar complexity of genetic dependencies in pediatric cancer cell lines compared to that in adult models. Findings from the pediatric cancer dependency map provide preclinical support for ongoing precision medicine clinical trials. The vulnerabilities observed in pediatric cancers were often distinct from those in adult cancer, indicating that repurposing adult oncology drugs will be insufficient to address childhood cancers.
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Children Successfully MATCHed to Therapies
(2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-nb2019-059 · Cited by 6 · see citing works
Morozova, O., Newton, Y., Cline, M., et al. (2015) · Cancer Research · doi:10.1158/1538-7445.am2015-lb-212 · Cited by 4 · see citing works
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Research works printed but not linked: 1
- [27]Dempster JM Extracting Biological Insights from the Project Achilles Genome-Scale CRISPR Screens in Cancer Cell Lines. bioRxiv 20, 720243 (2019).
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Beird, H. C., Bielack, S. S., Flanagan, A. M., Gill, J., Heymann, D., Janeway, K. A., Livingston, J. A., Roberts, R. D., Strauss, S. J., & Gorlick, R. (2022) · Nature Reviews Disease Primers · doi:10.1038/s41572-022-00409-y · Cited by 660 · see citing works
- Authors
- Dharia, N. V., Kugener, G., Guenther, L. M., Malone, C. F., Durbin, A. D., Hong, A. L., Howard, T. P., Bandopadhayay, P., Wechsler, C. S., Fung, I., Warren, A. C., Dempster, J. M., Krill-Burger, J. M., Paolella, B. R., Moh, P., Jha, N., Tang, A., Montgomery, P., Boehm, J. S., Hahn, W. C., Roberts, C. W. M., McFarland, J. M., Tsherniak, A., Golub, T. R., Vazquez, F., & Stegmaier, K.
- Affiliations
- Broad Institute (US)
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Stegmaier, Kimberly
- ORCID
- Dharia, Neekesh V.
- Kugener, Guillaume
- Guenther, Lillian M.
- Malone, Clare F.
- Durbin, Adam D.
- Hong, Andrew L.
- Howard, Thomas P.
- Bandopadhayay, Pratiti
- Wechsler, Caroline S.
- Dempster, Joshua M.
- Krill-Burger, John M.
- Paolella, Brenton R.
- Moh, Phoebe
- Jha, Nishant
- Montgomery, Philip
- Boehm, Jesse S.
- Hahn, William C.
- Roberts, Charles W. M.
- McFarland, James M.
- Tsherniak, Aviad
- Golub, Todd R.
- Vazquez, Francisca
- Stegmaier, Kimberly
- Venue
- Nature Genetics
- Published
- 2021-03-22
- Volume
- 53
- Issue
- 4
- Pages
- 529-538
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC8049517
- OpenAlex
- W3137588420
- Cited by
- 153
- References
- 79
- Citations by year
- 2026: 20 · 2025: 25 · 2024: 45 · 2023: 25 · 2022: 22 · 2021: 16
- FWCI
- 10.84
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (R35 CA210030, R01 CA204915, P01 CA217959, R00CA201592, U01 CA176058)
- St. Baldrick’s Foundation (Robert J. Arceci Innovation Award, Julia’s Legacy of Hope Fellow)
- Damon Runyon Cancer Research Foundation (PST-20-18, DRSG-24-18)
- Rally Foundation
- Boston Children’s Hospital
- U.S. Department of Health & Human Services | National Institutes of Health (F32CA243266, T32GM007753, T32GM007226)
- Alex’s Lemonade Stand Foundation for Childhood Cancer
- CureSearch for Children’s Cancer
- American Society of Clinical Oncology
- American Cancer Society (MRSG-18-202-01)
- United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (W81XWH-19-1-0281)
- Pediatric Brain Tumor Foundation
- Four C’s Fund PMC Team Eradicate Team Sciarappa Strong (Jimmy Fund Walk) Alexandra Simpson Pediatric Research Fund
- Helen Gurley Brown Presidential Initiative Fellowship
- Team Sciarappa Strong
- Jared Branfman Sunflowers for Life Fund The Isabel V Marxuach Fund for Medulloblastoma Research
- NBTII Foundation
- Alexandra Simpson Pediatric Research Fund
- Slim Initiative in Genomic Medicine for the Americas (SIGMA), a joint U.S-Mexico project funded by the Carlos Slim Foundation Walter and Marina Bornhorst
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- childhood cancer, gene dependency, cancer cell lines, somatic mutations, drug repurposing, precision medicine, pediatric solid tumors, pediatric brain tumors, therapeutic target
- MeSH terms
- Gene Editing, CRISPR-Associated Protein 9, RNA, Guide, CRISPR-Cas Systems, Adult, Child, Chromosome Mapping, Humans, Mutation, Neoplasm Proteins, Neoplasms, Genome, Human, Gene Expression Regulation, Neoplastic, RNA, Guide, Kinetoplastida, Genetic Predisposition to Disease, Gene Expression Profiling, Cell Line, Tumor, Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Cas Systems
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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