| General information | Literature | Expression | Regulation | Mutation | Interaction |
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Basic Information |
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|---|---|
Gene ID | 4849 |
Name | CNOT3 |
Synonymous | LENG2|NOT3|NOT3H;CCR4-NOT transcription complex, subunit 3;CNOT3;CCR4-NOT transcription complex, subunit 3 |
Definition | CCR4-NOT transcription complex subunit 3|CCR4-associated factor 3|NOT3 (negative regulator of transcription 3, yeast) homolog|leukocyte receptor cluster member 2 |
Position | 19q13.4 |
Gene type | protein-coding |
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Title |
Abstract |
| Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia. | 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. |