期刊
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
卷 39, 期 7, 页码 568-575出版社
WILEY
DOI: 10.1111/j.1365-2362.2009.02146.x
关键词
Chronic lymphocytic leukaemia; gene expression profiling; real-time polymerase chain reaction; trisomy 12
资金
- Austrian Ministry of Education, Science and Culture [GZ 200.136/1-VI/1/2005]
- Austrian Society of Hematology and Oncology
Background The prognosis of chronic lymphocytic leukaemia (CLL) patients is largely determined by the karyotype of the malignant clone. We have investigated the gene expression profile associated with trisomy 12 (+12). Design Initially, unselected peripheral blood mononuclear cells of four patients with +12 were compared with 16 CLL controls using microarray analysis. Results were validated by quantitative real-time PCR with RNA from 61 patients (29 with +12, 32 CLL controls). Results Seven genes showing the strongest correlation with +12 in microarray analysis were selected for real-time PCR: HIP1R, MYF6, SLC2A6, CD9 (overexpressed); CD200, P2RY14, RASGRP3 (underexpressed). Four genes were significantly associated with +12: HIP1R (P < 0 0001), MYF6 (P = 0 007), P2RY14 (P = 0 014), CD200 (P = 0 028). Receiver Operating Characteristic curve analysis revealed that HIP1R expression was a highly sensitive and specific marker for +12 in CLL patients. MYF6 was exclusively expressed in normal or malignant B cells in peripheral blood but was poorly predictive for +12. As expected, a number of overexpressed genes are located on chromosome 12 (HIP1R, MYF6). Interestingly, both significantly underexpressed genes (P2RY14, CD200) reside on the long arm of chromosome 3 pointing to trans-repression in this region. Conclusions Analysis of the molecular signature of trisomy 12 in CLL resulted in: (i) identification of a surrogate marker for PCR (HIP1R); (ii) observation of a gene dosage effect; and (iii) detection of specific underexpression of genes located on chromosome 3. These results should help to improve diagnosis and treatment decisions for patients with CLL and trisomy 12.
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