| Autor: |
Vasmatzis G; Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA., Johnson SH, Knudson RA, Ketterling RP, Braggio E, Fonseca R, Viswanatha DS, Law ME, Kip NS, Ozsan N, Grebe SK, Frederick LA, Eckloff BW, Thompson EA, Kadin ME, Milosevic D, Porcher JC, Asmann YW, Smith DI, Kovtun IV, Ansell SM, Dogan A, Feldman AL |
| Jazyk: |
angličtina |
| Zdroj: |
Blood [Blood] 2012 Sep 13; Vol. 120 (11), pp. 2280-9. Date of Electronic Publication: 2012 Aug 01. |
| DOI: |
10.1182/blood-2012-03-419937 |
| Abstrakt: |
Peripheral T-cell lymphomas (PTCLs) are aggressive malignancies of mature T lymphocytes with 5-year overall survival rates of only ∼ 35%. Improvement in outcomes has been stymied by poor understanding of the genetics and molecular pathogenesis of PTCL, with a resulting paucity of molecular targets for therapy. We developed bioinformatic tools to identify chromosomal rearrangements using genome-wide, next-generation sequencing analysis of mate-pair DNA libraries and applied these tools to 16 PTCL patient tissue samples and 6 PTCL cell lines. Thirteen recurrent abnormalities were identified, of which 5 involved p53-related genes (TP53, TP63, CDKN2A, WWOX, and ANKRD11). Among these abnormalities were novel TP63 rearrangements encoding fusion proteins homologous to ΔNp63, a dominant-negative p63 isoform that inhibits the p53 pathway. TP63 rearrangements were seen in 11 (5.8%) of 190 PTCLs and were associated with inferior overall survival; they also were detected in 2 (1.2%) of 164 diffuse large B-cell lymphomas. As TP53 mutations are rare in PTCL compared with other malignancies, our findings suggest that a constellation of alternate genetic abnormalities may contribute to disruption of p53-associated tumor suppressor function in PTCL. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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