title: Expression analysis of genes located in the minimally deleted regions of 13q14 and 11q22-23 in chronic lymphocytic leukemia-unexpected expression pattern of the RHO GTPase activator ARHGAP20.
abstract: In chronic lymphocytic leukemia (CLL), 13q14 and 11q22-23 deletions are found in 2/3 of the cases. 11q22-23 deletions are associated with poor survival, whereas 13q14 deletions as single abnormality are often found in indolent disease forms. The molecular basis for this difference in prognosis is not known. We examined the 13q14 and 11q22-23 minimally deleted regions (MDRs) for differentially expressed genes by analyzing 154 microarray CLL gene expression data sets. We were able to generate a detailed gene expression map of the MDRs demonstrating a gene dosage effect. Surprisingly, ARHGAP20 encoding the RHO GTPase activating protein 20, which is located in the 11q22-23 MDR, showed-counterintuitively-a significantly higher expression in cases with 11q22-23 deletions compared with cases with no detectable genetic lesion or trisomy 12. Interestingly, cases with 13q14 deletions also had higher ARHGAP20 expression. These expression level changes were confirmed by quantitative PCR in 110 additional CLL samples. The ARHGAP20 gene encodes an evolutionarily conserved protein. In the zebra fish (Danio rerio) genome the syntenic regions of human chromosomal bands 13q14 and 11q22-23 are juxtaposed. The similar expression profiles of ARHGAP20 in 13q14 and 11q22-23 deleted CLL cases suggest a molecular connection and an intriguing mechanism of regulation.
authors.affiliation: Department of Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Herold
authors.forename: Vindi
authors.initials: V
authors.lastname: Jurinovic
authors.forename: Medhanie
authors.initials: M
authors.lastname: Mulaw
authors.forename: Till
authors.initials: T
authors.lastname: Seiler
authors.forename: Annika
authors.initials: A
authors.lastname: Dufour
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schneider
authors.forename: Purvi M
authors.initials: PM
authors.lastname: Kakadia
authors.forename: Michaela
authors.initials: M
authors.lastname: Feuring-Buske
authors.forename: Jan
authors.initials: J
authors.lastname: Braess
authors.forename: Karsten
authors.initials: K
authors.lastname: Spiekermann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mansmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.forename: Christian
authors.initials: C
authors.lastname: Buske
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Bohlander
mesh_terms: D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D020690:GTPase-Activating Proteins / Q000235:genetics*; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C502036:ARHGAP20 protein, human; D020690:GTPase-Activating Proteins; D014157:Transcription Factors