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
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