Show simple item record

dc.contributor.authorAjore, Ramen_US
dc.contributor.authorRaiser, Daviden_US
dc.contributor.authorMcConkey, Marieen_US
dc.contributor.authorJöud, Magnusen_US
dc.contributor.authorBoidol, Bernden_US
dc.contributor.authorMar, Brentonen_US
dc.contributor.authorSaksena, Gordonen_US
dc.contributor.authorWeinstock, David Men_US
dc.contributor.authorArmstrong, Scotten_US
dc.contributor.authorEllis, Steven Ren_US
dc.contributor.authorEbert, Benjamin Len_US
dc.contributor.authorNilsson, Björnen_US
dc.date.accessioned2017-05-01T19:26:58Z
dc.date.issued2017en_US
dc.identifier.citationAjore, R., D. Raiser, M. McConkey, M. Jöud, B. Boidol, B. Mar, G. Saksena, et al. 2017. “Deletion of ribosomal protein genes is a common vulnerability in human cancer, especially in concert with TP53 mutations.” EMBO Molecular Medicine 9 (4): 498-507. doi:10.15252/emmm.201606660. http://dx.doi.org/10.15252/emmm.201606660.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:32630491
dc.description.abstractAbstract Heterozygous inactivating mutations in ribosomal protein genes (RPGs) are associated with hematopoietic and developmental abnormalities, activation of p53, and altered risk of cancer in humans and model organisms. Here we performed a large‐scale analysis of cancer genome data to examine the frequency and selective pressure of RPG lesions across human cancers. We found that hemizygous RPG deletions are common, occurring in about 43% of 10,744 cancer specimens and cell lines. Consistent with p53‐dependent negative selection, such lesions are underrepresented in TP53‐intact tumors (P ≪ 10−10), and shRNA‐mediated knockdown of RPGs activated p53 in TP53‐wild‐type cells. In contrast, we did not see negative selection of RPG deletions in TP53‐mutant tumors. RPGs are conserved with respect to homozygous deletions, and shRNA screening data from 174 cell lines demonstrate that further suppression of hemizygously deleted RPGs inhibits cell growth. Our results establish RPG haploinsufficiency as a strikingly common vulnerability of human cancers that associates with TP53 mutations and could be targetable therapeutically.en
dc.language.isoen_USen
dc.publisherJohn Wiley and Sons Inc.en
dc.relation.isversionofdoi:10.15252/emmm.201606660en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376749/pdf/en
dash.licenseLAAen_US
dc.subjectcanceren
dc.subjectribosomal gene haploinsufficiencyen
dc.subjectribosome functionen
dc.subjectCanceren
dc.subjectGenetics, Gene Therapy & Genetic Diseaseen
dc.titleDeletion of ribosomal protein genes is a common vulnerability in human cancer, especially in concert with TP53 mutationsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalEMBO Molecular Medicineen
dash.depositing.authorMar, Brentonen_US
dc.date.available2017-05-01T19:26:58Z
dc.identifier.doi10.15252/emmm.201606660*
dash.authorsorderedfalse
dash.contributor.affiliatedMar, Brenton
dash.contributor.affiliatedEbert, Benjamin


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record