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.
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 CLLpatients. 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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Authors: Erin Hertlein; Kyle A Beckwith; Gerard Lozanski; Timothy L Chen; William H Towns; Amy J Johnson; Amy Lehman; Amy S Ruppert; Brad Bolon; Leslie Andritsos; Arletta Lozanski; Laura Rassenti; Weiqiang Zhao; Tiina M Jarvinen; Leigha Senter; Carlo M Croce; David E Symer; Albert de la Chapelle; Nyla A Heerema; John C Byrd Journal: PLoS One Date: 2013-10-09 Impact factor: 3.240
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