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Title: Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia
Authors: De Keersmaecker, Kim *
Kalender Atak, Zeynep *
Li, Ning *
Vicente, Carmen
Patchett, Stephanie
Girardi, Tiziana
Gianfelici, Valentina
Geerdens, Ellen
Clappier, Emmanuelle
Porcu, Michaël
Lahortiga, Idoya
Lucà, Rossella
Yan, Jiekun
Hulselmans, Gert
Vranckx, Hilde
Vandepoel, Roel
Sweron, Bram
Jacobs, Kris
Mentens, Nicole
Wlodarska, Iwona
Cauwelier, Barbara
Cloos, Jacqueline
Soulier, Jean
Uyttebroeck, Anne
Bagni, Claudia
Hassan, Bassem A
Vandenberghe, Peter
Johnson, Arlen W
Aerts, Stein #
Cools, Jan # ×
Issue Date: Feb-2013
Publisher: Nature Publishing Group
Series Title: Nature Genetics vol:45 issue:2 pages:186-190
Article number: 10.1038/ng.2508
Abstract: 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.
URI: 
ISSN: 1061-4036
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory of Computational Biology
* (joint) first author
× corresponding author
# (joint) last author

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