MYC translocation and an increased copy number predict poor prognosis in adult diffuse large B-cell lymphoma (DLBCL), especially in germinal centre-like B cell (GCB) type

被引:112
作者
Yoon, S. O. [1 ,2 ]
Jeon, Y. K. [1 ,2 ]
Paik, J. H. [1 ,2 ]
Kim, W. Y. [1 ,2 ]
Kim, Y. A. [3 ]
Kim, J. E. [3 ]
Kim, C. W. [1 ,2 ]
机构
[1] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 110799, South Korea
[2] Seoul Natl Univ, Coll Med, Tumour Immun Med Res Ctr, Seoul 110799, South Korea
[3] Seoul Natl Univ, Boramae Hosp, Dept Pathol, Seoul, South Korea
关键词
Bcl-2; Bcl-6; chromosome translocation; diffuse large B cell lymphoma; MYC;
D O I
10.1111/j.1365-2559.2008.03076.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Aims: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with various genetic alterations. The aim was to investigate MYC, Bcl-2 and Bcl-6 translocations and copy number changes adult DLBCLs to evaluate their clinicopathological features and prognostic implications. Methods and results: Gene status was examined using fluorescence situ hybridization (FISH), and the results were analysed in the context of germinal centre B-cell (GCB) and non-GCB type of DLBCL based on immunohistochemistry. MYC translocation was observed in 9% (14 of 156), and an increased copy number (ICN) in 7.1% (11 of 156). MYC translocation was more common in GCB type (22%)) than in non-GCB type (4.9%), and associated with advanced International Prognostic Index (IPI). MYC aberration, i.e. translocation or increased copy number (ICN), was significantly associated with shorter overall survival, especially for the GCB type. Bcl-2 translocation was rare (3.4%. five of 145), and ICN was observed in 11.7%, (1.7 of 145). more frequently in non-GCB type (16%) than in GCB type (2.5%). Bcl-2 aberration tended to have an adverse effect on Survival. In multivariate analysis, MYC ICN was an independent poor prognostic factor. Conclusions: Analyses of MYC and Bcl-2 status. i.e. translocation and ICN, in the context of DLBCL phenotype might help predict prognosis and therapeutic strategies.
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页码:205 / 217
页数:13
相关论文
共 48 条
[1]  
AISENBERG AC, 1988, BLOOD, V71, P969
[2]   Molecular and clinical features of non-Burkitt's, diffuse large-cell lymphoma of B-cell type associated with the c-MYC/immunoglobulin heavy-chain fusion gene [J].
Akasaka, T ;
Akasaka, H ;
Ueda, C ;
Yonetani, N ;
Maesako, Y ;
Shimizu, A ;
Yamabe, H ;
Fukuhara, S ;
Uchiyama, T ;
Ohno, H .
JOURNAL OF CLINICAL ONCOLOGY, 2000, 18 (03) :510-518
[3]   Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling [J].
Alizadeh, AA ;
Eisen, MB ;
Davis, RE ;
Ma, C ;
Lossos, IS ;
Rosenwald, A ;
Boldrick, JG ;
Sabet, H ;
Tran, T ;
Yu, X ;
Powell, JI ;
Yang, LM ;
Marti, GE ;
Moore, T ;
Hudson, J ;
Lu, LS ;
Lewis, DB ;
Tibshirani, R ;
Sherlock, G ;
Chan, WC ;
Greiner, TC ;
Weisenburger, DD ;
Armitage, JO ;
Warnke, R ;
Levy, R ;
Wilson, W ;
Grever, MR ;
Byrd, JC ;
Botstein, D ;
Brown, PO ;
Staudt, LM .
NATURE, 2000, 403 (6769) :503-511
[4]   The spectrum of lymphoma with 8q24 aberrations: A clinical, pathological and cytogenetic study of 87 consecutive cases [J].
Au, WY ;
Horsman, DE ;
Gascoyne, RD ;
Viswanatha, DS ;
Klasa, RJ ;
Connors, JM .
LEUKEMIA & LYMPHOMA, 2004, 45 (03) :519-528
[5]   Diffuse large B-cell lymphomas with germinal center B-cell-like differentiation immunophenotypic profile are associated with high apoptotic index, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl [J].
Bai, M ;
Skyrlas, A ;
Agnantis, NJ ;
Kamina, S ;
Tsanou, E ;
Grepi, C ;
Galani, V ;
Kanavaros, P .
MODERN PATHOLOGY, 2004, 17 (07) :847-856
[6]  
Barrans SL, 2003, CLIN CANCER RES, V9, P2133
[7]  
BASTARD C, 1994, BLOOD, V83, P2423
[8]   Insights into the molecular pathogenesis of follicular lymphoma, arising from analysis of geographic variation [J].
Biagi, JJ ;
Seymour, JF .
BLOOD, 2002, 99 (12) :4265-4275
[9]   Translocations involving c-myc and c-myc function [J].
Boxer, LM ;
Dang, CV .
ONCOGENE, 2001, 20 (40) :5595-5610
[10]  
Chaganti RSK, 2000, SEMIN HEMATOL, V37, P396