例如:"lncRNA", "apoptosis", "WRKY"

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

Nat. Genet.2013 Feb;45(2):186-90. Epub 2012 Dec 23
Kim De Keersmaecker 1 , Zeynep Kalender Atak , Ning Li , Carmen Vicente , Stephanie Patchett , Tiziana Girardi , Valentina Gianfelici , Ellen Geerdens , Emmanuelle Clappier , Michaël Porcu , Idoya Lahortiga , Rossella Lucà , Jiekun Yan , Gert Hulselmans , Hilde Vranckx , Roel Vandepoel , Bram Sweron , Kris Jacobs , Nicole Mentens , Iwona Wlodarska , Barbara Cauwelier , Jacqueline Cloos , Jean Soulier , Anne Uyttebroeck , Claudia Bagni , Bassem A Hassan , Peter Vandenberghe , Arlen W Johnson , Stein Aerts , Jan Cools
Kim De Keersmaecker 1 , Zeynep Kalender Atak , Ning Li , Carmen Vicente , Stephanie Patchett , Tiziana Girardi , Valentina Gianfelici , Ellen Geerdens , Emmanuelle Clappier , Michaël Porcu , Idoya Lahortiga , Rossella Lucà , Jiekun Yan , Gert Hulselmans , Hilde Vranckx , Roel Vandepoel , Bram Sweron , Kris Jacobs , Nicole Mentens , Iwona Wlodarska , Barbara Cauwelier , Jacqueline Cloos , Jean Soulier , Anne Uyttebroeck , Claudia Bagni , Bassem A Hassan , Peter Vandenberghe , Arlen W Johnson , Stein Aerts , Jan Cools
+ et al

[No authors listed]

Author information
  • 1 Center for Human Genetics, KU Leuven, Leuven, Belgium.

摘要


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.