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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
Date Published2021 Mar 22
ISSN1546-1718
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

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

Alternate JournalNat Genet
PubMed ID33753930
Grant ListR35 CA210030 / CA / NCI NIH HHS / United States
R01 CA204915 / CA / NCI NIH HHS / United States
P01 CA217959 / CA / NCI NIH HHS / United States
R00CA201592 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
U01 CA176058 / CA / NCI NIH HHS / United States
Robert J. Arceci Innovation Award / / St. Baldrick's Foundation (St. Baldrick's Foundation, Inc) /
Julia's Legacy of Hope Fellow / / St. Baldrick's Foundation (St. Baldrick's Foundation, Inc) /
PST-20-18 / / Damon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation) /
DRSG-24-18 / / Damon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation) /
F32CA243266 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
T32GM007753 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
T32GM007226 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
MRSG-18-202-01 / / American Cancer Society (American Cancer Society, Inc.) /
W81XWH-19-1-0281 / / United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP) /