Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: Report from an International DLBCL Rituximab-CHOP Consortium Program Study Journal Article
| Authors: | Xu-Monette, Z. Y.; Wu, L.; Visco, C.; Tai, Y. C.; Tzankov, A.; Liu, W. M.; Montes-Moreno, S.; Dybkær, K.; Chiu, A.; Orazi, A.; Zu, Y.; Bhagat, G.; Richards, K. L.; Hsi, E. D.; Zhao, X. F.; Choi, W. W. L.; Zhao, X.; van Krieken, J. H.; Huang, Q.; Huh, J.; Ai, W.; Ponzoni, M.; Ferreri, A. J. M.; Zhou, F.; Kahl, B. S.; Winter, J. N.; Xu, W.; Li, J.; Go, R. S.; Li, Y.; Piris, M. A.; Møller, M. B.; Miranda, R. N.; Abruzzo, L. V.; Medeiros, L. J.; Young, K. H. |
| Article Title: | Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: Report from an International DLBCL Rituximab-CHOP Consortium Program Study |
| Abstract: | TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. In the present study of a large cohort of DLBCL patients treated with rituximab plus CHOP (R-CHOP), we show that those with TP53 mutations had worse overall and progression-free survival compared with those without. Unlike earlier studies of patients treated with CHOP, TP53 mutation has predictive value for R-CHOP- treated patients with either the germinal center B-cell or activated B-cell DLBCL subtypes. Furthermore, we identified the loop-sheet-helix and L3 motifs in the DNAbinding domain to be the most critical structures for maintaining p53 function. In contrast, TP53 deletion and loss of heterozygosity did not confer worse survival. If gene mutation data are not available, immunohistochemical analysis showing > 50% cells expressing p53 protein is a useful surrogate and was able to stratify patients with significantly different prognoses. We conclude that assessment of TP53 mutation status is important for stratifying R-CHOP-treated patients into distinct prognostic subsets and has significant value in the design of future therapeutic strategies. © 2012 by The American Society of Hematology. |
| Keywords: | immunohistochemistry; adult; controlled study; protein expression; treatment outcome; treatment response; aged; middle aged; dna binding protein; gene mutation; major clinical study; overall survival; gene deletion; mutation; exons; mutation, missense; prednisone; clinical feature; doxorubicin; cancer combination chemotherapy; disease marker; rituximab; neoplasm staging; protein domain; protein function; protein motif; progression free survival; cohort studies; gene expression profiling; computational biology; antineoplastic combined chemotherapy protocols; alleles; cyclophosphamide; vincristine; practice guideline; protein p53; prednisolone; gene expression regulation, neoplastic; nucleotide sequence; tumor suppressor protein p53; heterozygosity loss; large cell lymphoma; lymphoma, large b-cell, diffuse; mutation rate; loss of heterozygosity; helix loop helix protein; antibodies, monoclonal, murine-derived; cancer prognosis |
| Journal Title: | Blood |
| Volume: | 120 |
| Issue: | 19 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2012-11-08 |
| Start Page: | 3986 |
| End Page: | 3996 |
| Language: | English |
| DOI: | 10.1182/blood-2012-05-433334 |
| PROVIDER: | scopus |
| PUBMED: | 22955915 |
| PMCID: | PMC3496956 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 3 December 2012" - "CODEN: BLOOA" - "Source: Scopus" |
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