MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy:a report from the international DLBCL rituximab-CHOP consortium program
| العنوان: | MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy:a report from the international DLBCL rituximab-CHOP consortium program |
|---|---|
| المؤلفون: | L. Jeffrey Medeiros, William W.L. Choi, Eric D. Hsi, Weiyun Z. Ai, Sa A. Wang, Youli Zu, Yong Li, Govind Bhagat, Carlos E. Bueso-Ramos, Andrés J.M. Ferreri, Alexander Tzankov, Qin Huang, Ronald S. Go, Michael Boe Møller, Kristy L. Richards, Zijun Y. Xu-Monette, Miguel A. Piris, Santiago Montes-Moreno, Carlo Visco, April Chiu, Xiaoying Zhao, J. Han van Krieken, Jooryung Huh, Louise Kristensen, Wenwei Hu, Maurilio Ponzoni, Ken H. Young, Lin Wu, Karen Dybkær, Jane N. Winter, Lei Fan, Wayne Tam, Ganiraju C. Manyam |
| المساهمون: | Xu Monette, Zy, Møller, Mb, Tzankov, A, Montes Moreno, S, Hu, W, Manyam, Gc, Kristensen, L, Fan, L, Visco, C, Dybkaer, K, Chiu, A, Tam, W, Zu, Y, Bhagat, G, Richards, Kl, Hsi, Ed, Choi, Ww, van Krieken, Jh, Huang, Q, Huh, J, Ai, W, Ponzoni, Maurilio, Ferreri, Aj, Wu, L, Zhao, X, Bueso Ramos, Ce, Wang, Sa, Go, R, Li, Y, Winter, Jn, Piris, Ma, Medeiros, Lj, Young, Kh |
| المصدر: | Xu-Monette, Z Y, Møller, M, Tzankov, A, Montes-Moreno, S, Hu, W, Manyam, G C, Kristensen, L, Fan, L, Visco, C, Dybkær, K, Chiu, A, Tam, W, Zu, Y, Bhagat, G, Richards, K L, Hsi, E D, Choi, W W L, van Krieken, J H, Huang, Q, Huh, J, Ai, W, Ponzoni, M, Ferreri, A J M, Winter, J N, Wu, L, Zhao, X, Go, R S, Wang, S A, Bueso-Ramos, C E, Li, Y, Piris, M A, Medeiros, L J & Young, K H 2013, ' MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy : a report from the international DLBCL rituximab-CHOP consortium program ', Blood, vol. 122, no. 15, pp. 2630-2640 . https://doi.org/10.1182/blood-2012-12-473702Test Blood, 122, 15, pp. 2630-40 Xu-Monette, Z Y, Møller, M B, Tzankov, A, Montes-Moreno, S, Hu, W, Manyam, G C, Kristensen, L, Fan, L, Visco, C, Dybkaer, K, Chiu, A, Tam, W, Zu, Y, Bhagat, G, Richards, K L, Hsi, E D, Choi, W W L, van Krieken, J H, Huang, Q, Huh, J, Ai, W, Ponzoni, M, Ferreri, A J M, Wu, L, Zhao, X, Bueso-Ramos, C E, Wang, S A, Go, R S, Li, Y, Winter, J N, Piris, M A, Medeiros, L J & Young, K H 2013, ' MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy : a report from the International DLBCL Rituximab-CHOP Consortium Program ', Blood, vol. 122, no. 15, pp. 2630-40 . https://doi.org/10.1182/blood-2012-12-473702Test Blood, 122, 2630-40 Scopus-Elsevier |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, CHOP, Biochemistry, Antibodies, Monoclonal, Murine-Derived, immune system diseases, Risk Factors, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, P53-MDM2 FEEDBACK LOOP, MUTANT P53, IN-VIVO, Lymphoid Neoplasia, medicine.diagnostic_test, ONCOPROTEIN MDM2, Proto-Oncogene Proteins c-mdm2, Hematology, Middle Aged, Translational research Tissue engineering and pathology [ONCOL 3], Phenotype, Treatment Outcome, Vincristine, SURVIVAL, Rituximab, Female, Lymphoma, Large B-Cell, Diffuse, medicine.drug, SINGLE NUCLEOTIDE POLYMORPHISM, EXPRESSION, Adult, Genotype, Immunology, Single-nucleotide polymorphism, Biology, medicine, OSCILLATIONS, Humans, Immunologic Factors, NON-HODGKINS-LYMPHOMA, neoplasms, Cyclophosphamide, Aged, Gene Expression Profiling, OVEREXPRESSION, Cell Biology, medicine.disease, Lymphoma, Gene expression profiling, enzymes and coenzymes (carbohydrates), Doxorubicin, Cancer research, Prednisone, Tumor Suppressor Protein p53, Diffuse large B-cell lymphoma, Fluorescence in situ hybridization, Follow-Up Studies |
| الوصف: | MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53-genetically defined large cohort of de novo DLBCL patients treated with R-CHOP chemotherapy, we assessed MDM2 and p53 expression by immunohistochemistry (n=478), MDM2 gene amplification by fluorescence in situ hybridization (n=364), and a single nucleotide polymorphism in the MDM2 promoter, SNP309, by SNP genotyping assay (n=108). Our results show that MDM2 overexpression, unlike p53 overexpression, is not a significant prognostic factor in overall DLBCL. Both MDM2 and p53 overexpression does not predict for an adverse clinical outcome in patients with wild-type p53, but predicts for significantly poorer survival in patients with mutated p53. Variable p53 activities may ultimately determine the survival differences as suggested by the gene expression profiling analysis. MDM2 amplification was observed in 3 of 364 (0.8%) patients with high MDM2 expression. Presence of SNP309 did not correlate with MDM2 expression and survival. This study indicates that evaluation of MDM2 and p53 expression correlating with TP53 genetic status is essential to assess their prognostic significance, and important for designing therapeutic strategies that target the MDM2-p53 interaction. MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53-genetically defined large cohort of de novo DLBCL patients treated with R-CHOP chemotherapy, we assessed MDM2 and p53 expression by immunohistochemistry (n=478), MDM2 gene amplification by fluorescence in situ hybridization (n=364), and a single nucleotide polymorphism in the MDM2 promoter, SNP309, by SNP genotyping assay (n=108). Our results show that MDM2 overexpression, unlike p53 overexpression, is not a significant prognostic factor in overall DLBCL. Both MDM2 and p53 overexpression does not predict for an adverse clinical outcome in patients with wild-type p53, but predicts for significantly poorer survival in patients with mutated p53. Variable p53 activities may ultimately determine the survival differences as suggested by the gene expression profiling analysis. MDM2 amplification was observed in 3 of 364 (0.8%) patients with high MDM2 expression. Presence of SNP309 did not correlate with MDM2 expression and survival. This study indicates that evaluation of MDM2 and p53 expression correlating with TP53 genetic status is essential to assess their prognostic significance, and important for designing therapeutic strategies that target the MDM2-p53 interaction. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0006-4971 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d149c10c8f9f2acc9bf18a9031e3da0Test https://vbn.aau.dk/da/publications/1d9153ca-1a22-400c-aeab-76caec16a927Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8d149c10c8f9f2acc9bf18a9031e3da0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00064971 |
|---|