Combining MYC, BCL2 and TP53 gene and protein expression alterations improves risk stratification in diffuse large B-cell lymphoma

被引：13

作者：

Fiskvik, Idun ^{[1
,6
]}

Beiske, Klaus ^{[2
]}

Delabie, Jan ^{[7
]}

Yri, Olav ^{[8
]}

Spetalen, Signe ^{[2
]}

Karjalainen-Lindsberg, Marja-Liisa ^{[9
]}

Leppa, Sirpa ^{[10
]}

Liestol, Knut ^{[4
]}

Smeland, Erlend B. ^{[1
,5
]}

Holte, Harald ^{[3
,5
]}

机构：

[1] Inst Canc Res, Dept Immunol, N-0379 Oslo, Norway

[2] Oslo Univ Hosp, Dept Pathol, Oslo, Norway

[3] Oslo Univ Hosp, Dept Oncol, Oslo, Norway

[4] Univ Oslo, Dept Informat, N-0316 Oslo, Norway

[5] Univ Oslo, Ctr Canc Biomed, N-0316 Oslo, Norway

[6] Univ Oslo, N-0316 Oslo, Norway

[7] Univ Toronto, Dept Pathol, Toronto, ON M5S 1A1, Canada

[8] Akershus Univ Hosp, Dept Oncol, Lorenskog, Norway

[9] Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland

[10] Univ Helsinki, Cent Hosp, Ctr Canc, Dept Oncol, FIN-00014 Helsinki, Finland

来源：

LEUKEMIA & LYMPHOMA | 2015年 / 56卷 / 06期

关键词：

Lymphoma; DLBCL; double-hit; prognosis; CHOP CONSORTIUM PROGRAM; NON-HODGKINS-LYMPHOMA; RITUXIMAB PLUS CYCLOPHOSPHAMIDE; POOR-PROGNOSIS; R-CHOP; STRONG PREDICTOR; TRANSLOCATIONS; SURVIVAL; MUTATIONS; FEATURES;

D O I：

10.3109/10428194.2014.970550

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Translocations affecting both MYC and BCL2 are associated with a poor prognosis in diffuse large B-cell lymphomas. We have examined genetic aberrations combined with analyses of protein expression of respective gene products. Fluorescence in situ hybridization (FISH) for translocations of BCL2 and MYC and del17p13 was performed. Immunohistochemistry analyses included BCL2, MYC and TP53 protein expression. Sixty-seven patients with high-risk DLBCL participating in a prospective multicenter study were included. Six patients with simultaneous translocations of BCL2 and MYC had impaired overall (OS) (p = 0.009) and progression-free survival (PFS) (p= 0.009). Six patients with high coexpression of MYC and BCL2 proteins also had impaired OS (p = 0.004) and PFS (p = 0.002). Combining these groups identified nine patients with impaired OS (p= 0.004) and PFS (p= 0.005). Sixteen patients had double-hit translocation or protein expression and/or del17p13 and/or high TP53. This combined endpoint was associated with impaired OS (p= 0.008) and PFS (p= 0.036), and identified 70% of all deaths.

引用

页码：1742 / 1749

页数：8

共 48 条

[41] Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: a report from an International DLBCL rituximab-CHOP Consortium Program Study [J].

Visco, Carlo ;

Tzankov, Alexander ;

Xu-Monette, Zijun Y. ;

Miranda, Roberto N. ;

Tai, Yu Chuan ;

Li, Yan ;

Liu, Wei-min ;

d'Amore, Emanuele S. G. ;

Li, Yong ;

Montes-Moreno, Santiago ;

Dybkaer, Karen ;

Chiu, April ;

Orazi, Attilio ;

Zu, Youli ;

Bhagat, Govind ;

Wang, Huan-You ;

Dunphy, Cherie H. ;

His, Eric D. ;

Zhao, X. Frank ;

Choi, William W. L. ;

Zhao, Xiaoying ;

van Krieken, J. Han ;

Huang, Qin ;

Ai, Weiyun ;

O'Neill, Stacey ;

Ponzoni, Maurilio ;

Ferreri, Andres J. M. ;

Kahl, Brad S. ;

Winter, Jane N. ;

Go, Ronald S. ;

Dirnhofer, Stephan ;

Piris, Miguel A. ;

Moller, Michael B. ;

Wu, Lin ;

Medeiros, L. Jeffrey ;

Young, Ken H. .

HAEMATOLOGICA, 2013, 98 (02) :255-263

[42] Expression of p21 Protein Predicts Clinical Outcome in DLBCL Patients Older than 60 Years Treated with R-CHOP but not CHOP: A Prospective ECOG and Southwest Oncology Group Correlative Study on E4494 [J].

Winter, Jane N. ;

Li, Shuli ;

Aurora, Vikas ;

Variakojis, Daina ;

Nelson, Beverly ;

Krajewska, Maryla ;

Zhang, Lijun ;

Habermann, Thomas M. ;

Fisher, Richard I. ;

Macon, William R. ;

Chhanabhai, Mukesh ;

Felgar, Raymond E. ;

Hsi, Eric D. ;

Medeiros, L. Jeffrey ;

Weick, James K. ;

Weller, Edie A. ;

Melnick, Ari ;

Reed, John C. ;

Horning, Sandra J. ;

Gascoyne, Randy D. .

CLINICAL CANCER RESEARCH, 2010, 16 (08) :2435-2442

[43] 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 [J].

Xu-Monette, Zijun Y. ;

Moller, Michael B. ;

Tzankov, Alexander ;

Montes-Moreno, Santiago ;

Hu, Wenwei ;

Manyam, Ganiraju C. ;

Kristensen, Louise ;

Fan, Lei ;

Visco, Carlo ;

Dybkaer, Karen ;

Chiu, April ;

Tam, Wayne ;

Zu, Youli ;

Bhagat, Govind ;

Richards, Kristy L. ;

Hsi, Eric D. ;

Choi, William W. L. ;

van Krieken, J. Han ;

Huang, Qin ;

Huh, Jooryung ;

Ai, Weiyun ;

Ponzoni, Maurilio ;

Ferreri, Andres J. M. ;

Wu, Lin ;

Zhao, Xiaoying ;

Bueso-Ramos, Carlos E. ;

Wang, Sa A. ;

Go, Ronald S. ;

Li, Yong ;

Winter, Jane N. ;

Piris, Miguel A. ;

Medeiros, L. Jeffrey ;

Young, Ken H. .

BLOOD, 2013, 122 (15) :2630-2640

[44] 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].

Xu-Monette, Zijun Y. ;

Wu, Lin ;

Visco, Carlo ;

Tai, Yu Chuan ;

Tzankov, Alexander ;

Liu, Wei-min ;

Montes-Moreno, Santiago ;

Dybkaer, Karen ;

Chiu, April ;

Orazi, Attilio ;

Zu, Youli ;

Bhagat, Govind ;

Richards, Kristy L. ;

Hsi, Eric D. ;

Zhao, X. Frank ;

Choi, William W. L. ;

Zhao, Xiaoying ;

van Krieken, J. Han ;

Huang, Qin ;

Huh, Jooryung ;

Ai, Weiyun ;

Ponzoni, Maurilio ;

Ferreri, Andres J. M. ;

Zhou, Fan ;

Kahl, Brad S. ;

Winter, Jane N. ;

Xu, Wei ;

Li, Jianyong ;

Go, Ronald S. ;

Li, Yong ;

Piris, Miguel A. ;

Moller, Michael B. ;

Miranda, Roberto N. ;

Abruzzo, Lynne V. ;

Medeiros, L. Jeffrey ;

Young, Ken H. .

BLOOD, 2012, 120 (19) :3986-3996

[45] Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies [J].

Xu-Monette, Zijun Y. ;

Medeiros, L. Jeffrey ;

Li, Yong ;

Orlowski, Robert Z. ;

Andreeff, Michael ;

Bueso-Ramos, Carlos E. ;

Greiner, Timothy C. ;

McDonnell, Timothy J. ;

Young, Ken H. .

BLOOD, 2012, 119 (16) :3668-3683

[46] Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma:: an international collaborative study [J].

Young, Ken H. ;

Leroy, Karen ;

Moller, Michael B. ;

Colleoni, Gisele W. B. ;

Sanchez-Beato, Margarita ;

Kerbauy, Fabio R. ;

Haioun, Corinne ;

Eickhoff, Jens C. ;

Young, Allen H. ;

Gaulard, Philippe ;

Piris, Miguel A. ;

Oberley, Terry D. ;

Rehrauer, William M. ;

Kahl, Brad S. ;

Malter, James S. ;

Campo, Elias ;

Delabie, Jan ;

Gascoyne, Randy D. ;

Rosenwald, Andreas ;

Rimsza, Lisa ;

Huang, James ;

Braziel, Rita M. ;

Jaffe, Elaine S. ;

Wilson, Wyndham H. ;

Staudt, Louis M. ;

Vose, Julie M. ;

Chan, Wing C. ;

Weisenburger, Dennis D. ;

Greiner, Timothy C. .

BLOOD, 2008, 112 (08) :3088-3098

[47] Mutations in the DNA-binding codons of TP53, which are associated with decreased expression of TRAIL receptor-2, predict for poor survival in diffuse large B-cell lymphoma [J].

Young, Ken H. ;

Weisenburger, Dennis D. ;

Dave, Bhavana J. ;

Smith, Lynette ;

Sanger, Warren ;

Iqbal, Javeed ;

Campo, Elias ;

Delabie, Jan ;

Gascoyne, Randy D. ;

Ott, German ;

Rimsza, Lisa ;

Mueller-Hermelink, H. Konrad ;

Jaffe, Elaine S. ;

Rosenwald, Andreas ;

Staudt, Louis M. ;

Chan, Wing C. ;

Greiner, Timothy C. .

BLOOD, 2007, 110 (13) :4396-4405

[48] Standard International Prognostic Index Remains a Valid Predictor of Outcome for Patients With Aggressive CD20+ B-Cell Lymphoma in the Rituximab Era [J].

Ziepert, Marita ;

Hasenclever, Dirk ;

Kuhnt, Evelyn ;

Glass, Bertram ;

Schmitz, Norbert ;

Pfreundschuh, Michael ;

Loeffler, Markus .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (14) :2373-2380

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