Loading...
Please wait, while we are loading the content...
Similar Documents
ATM mutations are associated with inactivation of theARF-TP53 tumor suppressor pathway in diffuse large B-cell lymphoma
| Content Provider | Scilit |
|---|---|
| Author | Grønbæk, Kirsten Worm, Jesper Ralfkiaer, Elisabeth Ahrenkiel, Vibeke Hokland, Peter Guldberg, Per |
| Copyright Year | 2002 |
| Description | The ATM serine-threonine kinase plays a central role in the cellular response to DNA damage. Germ-line mutations in theATM gene cause ataxia-telangiectasia (A-T), a multisystem disorder associated with predisposition to lymphoma and acute leukemia. Moreover, somatic ATM mutations have been identified in T-cell prolymphocytic leukemia, mantle cell lymphoma, and B-cell chronic lymphocytic leukemia. In this study, the entire ATMcoding sequence was examined in genomic DNA from 120 lymphoid neoplasms. Novel mutations and mutations implicated in cancer and/or A-T were found in 9 of 45 diffuse large B-cell lymphomas (DLBCLs), 2 of 24 follicular lymphomas, and 1 of 27 adult acute lymphoblastic leukemias, whereas no such mutations were detected among 24 peripheral T-cell lymphomas. The mutational spectrum consisted of 2 nonsense mutations, 1 mutation affecting RNA splicing, and 10 missense variants. Most of these mutations were associated with loss or mutation of the paired ATM allele, consistent with biallelic inactivation of ATM. Of the 9 DLBCLs with ATM mutations, 7 also carried TP53 mutations and/or deletions of theINK4a/ARF locus (P = .003). TheATM 735C>T substitution previously considered a rare normal variant was found to be 5.6 times more frequent in individuals with DLBCL than in random individuals (P = .026), suggesting that it may predispose to B-cell lymphoma. Our data suggest that ATM mutations contribute to the development of DLBCL, and that ATM and the ARF-p53 tumor suppressor pathway may cooperate in the pathogenesis of this malignancy. |
| Related Links | http://bloodjournal.hematologylibrary.org/content/100/4/1430.full.pdf |
| Ending Page | 1437 |
| Page Count | 8 |
| Starting Page | 1430 |
| DOI | 10.1182/blood-2002-02-0382 |
| Journal | Blood |
| Issue Number | 4 |
| Volume Number | 100 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2002-08-15 |
| Access Restriction | Open |
| Subject Keyword | Hematology Diffuse Large B Cell Lymphomas Splicing Tp53 Tumor Suppressor Allele Atm Mutations Journal: Blood (Vol- 78, Issue- 4) |
| Content Type | Text |
| Resource Type | Article |
