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 DNA-binding 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.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
authors.forename: Zijun Y
authors.initials: ZY
authors.lastname: Xu-Monette
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.forename: Carlo
authors.initials: C
authors.lastname: Visco
authors.forename: Yu Chuan
authors.initials: YC
authors.lastname: Tai
authors.forename: Alexander
authors.initials: A
authors.lastname: Tzankov
authors.forename: Wei-min
authors.initials: WM
authors.lastname: Liu
authors.forename: Santiago
authors.initials: S
authors.lastname: Montes-Moreno
authors.forename: Karen
authors.initials: K
authors.lastname: Dybkaer
authors.forename: April
authors.initials: A
authors.lastname: Chiu
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
authors.forename: Youli
authors.initials: Y
authors.lastname: Zu
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
authors.forename: Kristy L
authors.initials: KL
authors.lastname: Richards
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: X Frank
authors.initials: XF
authors.lastname: Zhao
authors.forename: William W L
authors.initials: WW
authors.lastname: Choi
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhao
authors.forename: J Han
authors.initials: JH
authors.lastname: van Krieken
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
authors.forename: Jooryung
authors.initials: J
authors.lastname: Huh
authors.forename: Weiyun
authors.initials: W
authors.lastname: Ai
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.forename: Andrés J M
authors.initials: AJ
authors.lastname: Ferreri
authors.forename: Fan
authors.initials: F
authors.lastname: Zhou
authors.forename: Brad S
authors.initials: BS
authors.lastname: Kahl
authors.forename: Jane N
authors.initials: JN
authors.lastname: Winter
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Jianyong
authors.initials: J
authors.lastname: Li
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Go
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Piris
authors.forename: Michael B
authors.initials: MB
authors.lastname: Møller
authors.forename: Roberto N
authors.initials: RN
authors.lastname: Miranda
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Abruzzo
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D019295:Computational Biology; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005091:Exons; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D020125:Mutation, Missense; D009367:Neoplasm Staging; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D000069283:Rituximab; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D016159:Tumor Suppressor Protein p53; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone