دورية أكاديمية
Sequential mutations in Notch1, Fbxw7, and Tp53 in radiation-induced mouse thymic lymphomas.
| العنوان: | Sequential mutations in Notch1, Fbxw7, and Tp53 in radiation-induced mouse thymic lymphomas. |
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| المؤلفون: | Jen KY; Department of Pathology, University of California-San Francisco, USA., Song IY, Banta KL, Wu D, Mao JH, Balmain A |
| المصدر: | Blood [Blood] 2012 Jan 19; Vol. 119 (3), pp. 805-9. Date of Electronic Publication: 2011 Nov 23. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
| مواضيع طبية MeSH: | F-Box Proteins/*genetics , Mutation/*genetics , Neoplasms, Radiation-Induced/*etiology , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/*etiology , Receptor, Notch1/*genetics , Thymus Neoplasms/*etiology , Tumor Suppressor Protein p53/*genetics , Ubiquitin-Protein Ligases/*genetics, Animals ; Disease Models, Animal ; F-Box-WD Repeat-Containing Protein 7 ; Female ; Loss of Heterozygosity ; Male ; Mice ; Mice, Knockout ; Neoplasms, Radiation-Induced/pathology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Protein Structure, Tertiary ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Thymus Neoplasms/pathology |
| مستخلص: | T-cell acute lymphoblastic lymphomas commonly demonstrate activating Notch1 mutations as well as mutations or deletions in Fbxw7. However, because Fbxw7 targets Notch1 for degradation, genetic alterations in these genes are expected to be mutually exclusive events in lymphomagenesis. Previously, by using a radiation-induced Tp53-deficient mouse model for T-cell acute lymphoblastic lymphoma, we reported that loss of heterozygosity at the Fbxw7 locus occurs frequently in a Tp53-dependent manner. In the current study, we show that these thymic lymphomas also commonly exhibit activating Notch1 mutations in the proline-glutamic acid-serine-threonine (PEST) domain. Moreover, concurrent activating Notch1 PEST domain mutations and single-copy deletions at the Fbxw7 locus occur with high frequency in the same individual tumors, indicating that these changes are not mutually exclusive events. We further demonstrate that although Notch1 PEST domain mutations are independent of Tp53 status, they are completely abolished in mice with germline Fbxw7 haploinsufficiency. Therefore, Notch1 PEST domain mutations only occur when Fbxw7 expression levels are intact. These data suggest a temporal sequence of mutational events involving these important cancer-related genes, with Notch1 PEST domain mutations occurring first, followed by Fbxw7 deletion, and eventually by complete loss of Tp53. |
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| معلومات مُعتمدة: | R01 CA116481 United States CA NCI NIH HHS; T32 CA108462 United States CA NCI NIH HHS; U01 CA141455 United States CA NCI NIH HHS; 5T32 CA108462 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (F-Box Proteins) 0 (F-Box-WD Repeat-Containing Protein 7) 0 (Fbxw7 protein, mouse) 0 (Notch1 protein, mouse) 0 (RNA, Messenger) 0 (Receptor, Notch1) 0 (Tumor Suppressor Protein p53) EC 2.3.2.27 (Ubiquitin-Protein Ligases) |
| تواريخ الأحداث: | Date Created: 20111126 Date Completed: 20120313 Latest Revision: 20211021 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC3265203 |
| DOI: | 10.1182/blood-2011-01-327619 |
| PMID: | 22117044 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1528-0020 |
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| DOI: | 10.1182/blood-2011-01-327619 |