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Nat Genet DOI:10.1038/s41588-021-00819-w

A first-generation pediatric cancer dependency map.

Publication TypeJournal Article
Year of Publication2021
AuthorsDharia, NV, Kugener, G, Guenther, LM, Malone, CF, Durbin, AD, Hong, AL, Howard, TP, Bandopadhayay, P, Wechsler, CS, Fung, I, Warren, AC, Dempster, JM, Krill-Burger, JM, Paolella, BR, Moh, P, Jha, N, Tang, A, Montgomery, P, Boehm, JS, Hahn, WC, Roberts, CWM, McFarland, JM, Tsherniak, A, Golub, TR, Vazquez, F, Stegmaier, K
JournalNat Genet
Volume53
Issue4
Pages529-538
Date Published2021 04
ISSN1546-1718
KeywordsAdult, Cell Line, Tumor, Child, Chromosome Mapping, Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Associated Protein 9, CRISPR-Cas Systems, Gene Editing, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease, Genome, Human, Humans, Mutation, Neoplasm Proteins, Neoplasms, RNA, Guide
Abstract

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.

DOI10.1038/s41588-021-00819-w
Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/33753930?dopt=Abstract

Alternate JournalNat Genet
PubMed ID33753930
PubMed Central IDPMC8049517
Grant ListT32 GM007226 / GM / NIGMS NIH HHS / United States
P01 CA217959 / CA / NCI NIH HHS / United States
U01 CA176058 / CA / NCI NIH HHS / United States
F32 CA243266 / CA / NCI NIH HHS / United States
R00 CA201592 / CA / NCI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
K08 CA245251 / CA / NCI NIH HHS / United States
R35 CA210030 / CA / NCI NIH HHS / United States
R01 CA204915 / CA / NCI NIH HHS / United States