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
Institution
Titre
Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia.
Périodique
Nature genetics
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
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