RGD Reference Report - Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia.

Authors: De Keersmaecker, K  Atak, ZK  Li, N  Vicente, C  Patchett, S  Girardi, T  Gianfelici, V  Geerdens, E  Clappier, E  Porcu, M  Lahortiga, I  Luca, R  Yan, J  Hulselmans, G  Vranckx, H  Vandepoel, R  Sweron, B  Jacobs, K  Mentens, N  Wlodarska, I  Cauwelier, B  Cloos, J  Soulier, J  Uyttebroeck, A  Bagni, C  Hassan, BA  Vandenberghe, P  Johnson, AW  Aerts, S  Cools, J 
Citation: De Keersmaecker K, etal., Nat Genet. 2013 Feb;45(2):186-90. doi: 10.1038/ng.2508. Epub 2012 Dec 23.
RGD ID: 11535135
Pubmed: PMID:23263491   (View Abstract at PubMed)
PMCID: PMC5547913   (View Article at PubMed Central)
DOI: DOI:10.1038/ng.2508   (Journal Full-text)

T-cell acute lymphoblastic leukemia (T-ALL) is caused by the cooperation of multiple oncogenic lesions. We used exome sequencing on 67 T-ALLs to gain insight into the mutational spectrum in these leukemias. We detected protein-altering mutations in 508 genes, with an average of 8.2 mutations in pediatric and 21.0 mutations in adult T-ALL. Using stringent filtering, we predict seven new oncogenic driver genes in T-ALL. We identify CNOT3 as a tumor suppressor mutated in 7 of 89 (7.9%) adult T-ALLs, and its knockdown causes tumors in a sensitized Drosophila melanogaster model. In addition, we identify mutations affecting the ribosomal proteins RPL5 and RPL10 in 12 of 122 (9.8%) pediatric T-ALLs, with recurrent alterations of Arg98 in RPL10. Yeast and lymphoid cells expressing the RPL10 Arg98Ser mutant showed a ribosome biogenesis defect. Our data provide insights into the mutational landscape of pediatric versus adult T-ALL and identify the ribosome as a potential oncogenic factor.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
RPL5HumanT-cell acute lymphoblastic leukemia  IAGP DNA:snps more ...RGD 
Rpl5RatT-cell acute lymphoblastic leukemia  ISORPL5 (Homo sapiens)DNA:snps more ...RGD 
Rpl5MouseT-cell acute lymphoblastic leukemia  ISORPL5 (Homo sapiens)DNA:snps more ...RGD 


Genes (Rattus norvegicus)
Rpl5  (ribosomal protein L5)

Genes (Mus musculus)
Rpl5  (ribosomal protein L5)

Genes (Homo sapiens)
RPL5  (ribosomal protein L5)