title: Gene expression signature of chronic lymphocytic leukaemia with Trisomy 12.
abstract: 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).
  
  
  METHODS
  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.
authors.affiliation: Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Porpaczy
authors.forename: M
authors.initials: M
authors.lastname: Bilban
authors.forename: G
authors.initials: G
authors.lastname: Heinze
authors.forename: M
authors.initials: M
authors.lastname: Gruber
authors.forename: K
authors.initials: K
authors.lastname: Vanura
authors.forename: I
authors.initials: I
authors.lastname: Schwarzinger
authors.forename: S
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: B
authors.initials: B
authors.lastname: Streubel
authors.forename: C
authors.initials: C
authors.lastname: Fonatsch
authors.forename: U
authors.initials: U
authors.lastname: Jaeger
mesh_terms: D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007621:Karyotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D014314:Trisomy / Q000235:genetics / Q000473:pathology*