|Table of Contents|

Prognostic value of TP53 mutation and deletion on patients with DLBCL

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 03
Page:
518-523
Research Field:
Publishing date:

Info

Title:
Prognostic value of TP53 mutation and deletion on patients with DLBCL
Author(s):
GU Jia1; BAI Sijun2; GENG Ye2; HE Jianxia2
1.Department of Hematology,Jincheng People's Hospital，Shanxi Jincheng 048000，China;2.Department of Hematology,The Fifth Clinical Medical College of Shanxi Medical University,Shanxi Provincial People's Hospital,Shanxi Taiyuan 030012,China.
Keywords:
diffuse large B-cell lymphoma; TP53; mutation; deletion; prognosis
PACS:
R733.4
DOI:
10.3969/j.issn.1672-4992.2024.03.023
Abstract:
Objective:To investigate prognostic value of TP53 mutation and deletion on patients with diffuse large B-cell lymphoma(DLBCL).Methods:Paraffin pathological tissues of 94 newly diagnosed DLBCL patients in Shanxi Provincial People's Hospital from 2017 to 2020 were collected.TP53 mutations were detected by immunohistochemistry and next-generation sequencing,and was used to find TP53 deletions were detected by Fluorescence in situ hybridization(FISH).The correlation between TP53 mutations and deletions with clinicopathological and molecular typing,as well as the impact on survival were analyzed.Prognostic factors of DLBCL was analyze by COX regression.Results:27.7%(26/94) patients overexpressed p53,23.5%(19/81) patients had TP53 mutation,and 16.0%(15/94) patients had TP53 deletion.Extranodal involvement(P=0.027),MUM-1 expression(P=0.04) and p53(P<0.01) were significantly different between the group of TP53 mutation and/or deletion and the group of TP53 wildtype.Survival analysis revealed that the "double positive(TP53 mutations and deletion) " group had the worst survival,"double negative(TP53 wildtype)" group had best survival,TP53 mutations or deletions are followed.OS had significant statistical difference between each groups(P<0.05)，except that between TP53 mutation group and deletion group(P=0.689).In GCB,TP53 mutation group had shorter OS(P=0.046).Multivariate analysis showed that B symptoms,abnormal TP53 and double expression were independent risk factors for DLBCL survival.Conclusion:TP53 mutation or deletion,especially combined mutation and deletion,is a poor prognostic factor of DLBCL.The prognostic significance of TP53 mutation or deletion in new molecular subtype is worthy of further exploration.

References:

[1]INTLEKOFER AM,JOFFE E,BATLEVI CL,et al.Integrated DNA/RNA targeted genomic profiling of diffuse large B-cell lymphoma using a clinical assay［J］.Blood Cancer J,2018,8(6):60.
[2]YOUNG KH,LEROY K,MOLLER MB,et al.Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma:an international collaborative study［J］.Blood,2008,112(8):3088-3098.
[3]XU-MONETTE ZY,WU L,VISCO C,et al.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［J］.Blood,2012,120(19):3986-3996.
[4]DOBASHI A,TOGASHI Y,TANAKA N,et al.TP53 and OSBPL10 alterations in diffuse large B-cell lymphoma:prognostic markers identified via exome analysis of cases with extreme prognosis［J］.Oncotarget,2018,9(28):19555-19568.
[5]STEFANCIKOVA L,MOULIS M,FABIAN P,et al.Prognostic impact of p53 aberrations for R-CHOP-treated patients with diffuse large B-cell lymphoma［J］.Int J Oncol,2011,39(6):1413-1420.
[6]FISKVIK I,BEISKE K,DELABIE J,et al.Combining MYC,BCL2 and TP53 gene and protein expression alterations improves risk stratification in diffuse large B-cell lymphoma［J］.Leuk Lymphoma,2015,56(6):1742-1749.
[7]HU S,XU-MONETTE ZY,TZANKOV A,et al.MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures:a report from The International DLBCL Rituximab-CHOP Consortium Program［J］.Blood,2013,121(20):4021-4031.
[8]CAO Y,ZHU T,ZHANG P,et al.Mutations or copy number losses of CD58 and TP53 genes in diffuse large B cell lymphoma are independent unfavorable prognostic factors［J］.Oncotarget,2016,7(50):83294-83307.
[9]GIANNUZZI D,MARCONATO L,FANELLI A,et al.The genomic landscape of canine diffuse large B-cell lymphoma identifies distinct subtypes with clinical and therapeutic implications［J］.Lab Anim(NY),2022,51(7):191-202.
[10]EBID O,EZZ E AL,SAAD AS,et al.Prognostic impact of MYD88 and TP53 mutations in diffuse large B cell lymphoma［J］.Ann Hematol,2023,102(12):3477-3488.
[11]CHIAPPELLA A,DIOP F,AGOSTINELLI C,et al.Prognostic impact of TP53 mutation in newly diagnosed diffuse large B-cell lymphoma patients treated in the FIL-DLCL04 trial［J］.Br J Haematol,2022,196(5):1184-1193.
[12]HONG Y,REN T,WANG X,et al.APR-246 triggers ferritinophagy and ferroptosis of diffuse large B-cell lymphoma cells with distinct TP53 mutations［J］.Leukemia,2022,36(9):2269-2280.
[13]ZIVANOVIC A,STAMATOVIC D,STRELIC N,et al.Association of ATG16L1 rs2241880 and TP53 rs1042522 with characteristics and course of diffuse large B-cell lymphoma［J］.Pathol Res Pract,2022,237:154033.
[14]TESSOULIN B,EVEILLARD M,LOK A,et al.p53 dysregulation in B-cell malignancies:More than a single gene in the pathway to hell［J］.Blood Rev,2017,31(4):251-259.
[15]AMIR H,TOUBOUL T,SABATINI K,et al.Spontaneous single-copy loss of TP53 in human embryonic stem cells markedly increases cell proliferation and survival［J］.Stem Cells,2017,35(4):872-885.
[16]BEA S,COLOMO L,LOPEZ-GUILLERMO A,et al.Clinicopathologic significance and prognostic value of chromosomal imbalances in diffuse large B-cell lymphomas［J］.J Clin Oncol,2004,22(17):3498-3506.
[17]孙冠星,曹祥山,李青,等.BCL-6、MYC和p53基因异常与弥漫性大B细胞淋巴瘤免疫学亚型及预后的关系［J］.中华医学遗传学杂志,2012,29(5):576-581. SUN GX，CAO XS,LI Q,et al.Correlation of BCL-6,MYC and p53 gene abnormalities with immunological subtypes and prognosis of diffuse large B-cell lymphoma［J］.Chinese Journal of Medical Genetics,2012,29(5):576-581.
[18]LACY SE,BARRANS SL,BEER PA,et al.Targeted sequencing in DLBCL,molecular subtypes,and outcomes:a haematological malignancy research network report［J］.Blood,2020,135(20):1759-1771.
[19]GORDON MJ,WESTIN JR.Fitting double-hit lymphoma into the aggressive lymphoma spectrum:a square peg in a round hole［J］.Leuk Lymphoma,2022,63(5):1034-1044.
[20]LOPEZ-SANTILLAN M,LOPEZ-LOPEZ E,ALVAREZ-GONZALEZ P,et al.Prognostic and therapeutic value of somatic mutations in diffuse large B-cell lymphoma:A systematic review［J］.Crit Rev Oncol Hematol,2021,165:103430.
[21]WANG XJ,MEDEIROS LJ,BUESO-RAMOS CE,et al.p53 expression correlates with poorer survival and augments the negative prognostic effect of MYC rearrangement,expression or concurrent MYC/BCL2 expression in diffuse large B-cell lymphoma［J］.Mod Pathol,2017,30(2):194-203.
[22]RIEDELL PA,SMITH SM.Double hit and double expressors in lymphoma:Definition and treatment［J］.Cancer,2018,124(24):4622-4632.

Memo

Memo:
山西省自然科学基金(编号:201901D111435)
Last Update: 2023-12-29