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

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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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal 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 

Objects Annotated

Genes (Rattus norvegicus)
Rpl5  (ribosomal protein L5)

Genes (Mus musculus)
Rpl5  (ribosomal protein L5)

Genes (Homo sapiens)
RPL5  (ribosomal protein L5)


Additional Information