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

Détails

ID Serval
serval:BIB_63ACF28A8C65
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia.
Périodique
Nature genetics
Auteur⸱e⸱s
De Keersmaecker K., Atak Z.K., Li N., Vicente C., Patchett S., Girardi T., Gianfelici V., Geerdens E., Clappier E., Porcu M., Lahortiga I., Lucà 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 B.A., Vandenberghe P., Johnson A.W., Aerts S., Cools J.
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Statut éditorial
Publié
Date de publication
02/2013
Volume
45
Numéro
2
Pages
186-190
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.

Mots-clé
Animals, Base Sequence, Drosophila melanogaster, Exome/genetics, High-Throughput Nucleotide Sequencing, Humans, Mice, Molecular Sequence Data, Mutagenesis, Site-Directed, Mutation/genetics, Polyribosomes/genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics, RNA Interference, Ribosomal Proteins/genetics, Saccharomyces cerevisiae, Sequence Alignment, Transcription Factors/genetics
Pubmed
Création de la notice
06/03/2017 17:23
Dernière modification de la notice
20/08/2019 14:20
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