Genome-wide DNA analysis identifies recurrent imbalances predicting outcome in chronic lymphocytic leukaemia with 17p deletion

被引:52
作者
Forconi, Francesco [1 ]
Rinaldi, Andrea [2 ]
Kwee, Ivo [2 ,3 ]
Sozzi, Elisa [1 ]
Raspadori, Donatella [1 ]
Rancoita, Paola M. V. [2 ,3 ]
Scandurra, Marta [2 ]
Rossi, Davide [4 ,5 ]
Deambrogi, Clara [4 ,5 ]
Capello, Daniela [4 ,5 ]
Zucca, Emanuele [6 ]
Marconi, Daniela [5 ,7 ]
Bomben, Riccardo [7 ]
Gattei, Valter
Lauria, Francesco [1 ]
Gaidano, Gianluca [4 ,5 ]
Bertoni, Francesco [2 ]
机构
[1] Univ Siena, Dipartimento Med Clin & Sci Immunol, Sez Ematol & Trapianti, I-53100 Siena, Italy
[2] Oncol Inst So Switzerland, Expt Oncol Lab, Bellinzona, Switzerland
[3] Ist Dalle Molle Studi Intelligenza Artificiale, Manno, Switzerland
[4] Univ Piemonte Orientale Amedeo Avogadro, Dipartimento Genet Clin & Sperimentale, Div Ematol, Novara, Italy
[5] Univ Piemonte Orientale Amedeo Avogadro, BRMA, Novara, Italy
[6] Oncol Inst So Switzerland, Lymphoma Unit, Bellinzona, Switzerland
[7] IRCCS, Ctr Riferimento Oncol, Clin & Expt Oncohematol Unit, Aviano, PN, Italy
基金
瑞士国家科学基金会;
关键词
chronic lymphocytic leukaemia; 17p13; deletion; TP53; genome-wide DNA profile; 250K Affymetrix; single nucleotide polymporphysms;
D O I
10.1111/j.1365-2141.2008.07373.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Deletion of 17p (TP53) identifies a rare subset of chronic lymphocytic leukaemia (17p- CLL) with aggressive behaviour. Genome-wide DNA-profiling was performed to investigate 18 patients with 17p- CLL. All cases had multiple copy-number (CN) changes. Among the several recurrent CN changes identified, 8q24.13-q24.1-gain (MYC), 8p-loss (TNFRSF10A/B, also known as TRAIL1/2) and 2p16.1-p14-gain (REL/BCL11A) appeared frequently represented. 8p-loss and 2p16.1-p14-gain also appeared clinically relevant and predicted significant shorter time from diagnosis to treatment (8p-loss) and overall survival (8p-loss and 2p16.1-p14-gain, P < 0.05). These observations document a highly unstable genome in 17p- CLL and suggest that additional genes outside the TP53 locus may be important for tumour behaviour.
引用
收藏
页码:532 / 536
页数:5
相关论文
共 15 条
  • [11] Comprehensive biomarker and genomic analysis identifies p53 status as the major determinant of response to MDM2 inhibitors in chronic lymphocytic leukemia
    Saddler, Chris
    Ouillette, Peter
    Kujawski, Lisa
    Shangary, Sanjeev
    Talpaz, Moshe
    Kaminski, Mark
    Erba, Harry
    Shedden, Kerby
    Wang, Shaomeng
    Malek, Sami N.
    [J]. BLOOD, 2008, 111 (03) : 1584 - 1593
  • [12] Specific secondary genetic alterations in mantle cell lymphoma provide prognostic information independent of the gene expression-based proliferation signature
    Salaverria, Itziar
    Zettl, Andreas
    Bea, Silvia
    Moreno, Victor
    Valls, Joan
    Hartmann, Elena
    Ott, German
    Wright, George
    Lopez-Guillermo, Armando
    Chan, Wing C.
    Weisenburger, Dennis D.
    Gascoyne, Randy D.
    Grogan, Thomas M.
    Delabie, Jan
    Jaffe, Elaine S.
    Montserrat, Emili
    Muller-Hermelink, Hans-Konrad
    Staudt, Louis M.
    Rosenwald, Andreas
    Campo, Elias
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (10) : 1216 - 1222
  • [13] Automated array-based genomic profiling in chronic lymphocytic leukemia:: Development of a clinical tool and discovery of recurrent genomic alterations
    Schwaenen, C
    Nessling, M
    Wessendorf, S
    Salvi, T
    Wrobel, G
    Radlwimmer, B
    Kestler, HA
    Haslinger, C
    Stilgenbauer, S
    Döhner, H
    Bentz, M
    Lichter, P
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (04) : 1039 - 1044
  • [14] Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL)
    Secchiero, Paola
    Barbarotto, Elisa
    Tiribelli, Mario
    Zerbinati, Carlotta
    di Iasio, Maria Grazia
    Gonelli, Arianna
    Cavazzini, Francesco
    Campioni, Diana
    Fanin, Renato
    Cuneo, Antonio
    Zauli, Giorgio
    [J]. BLOOD, 2006, 107 (10) : 4122 - 4129
  • [15] VEELKEN H, 2007, LEUKAEMIA LYMPHOM S1, V48, pS3