Expression analysis of genes located in the minimally deleted regions of 13q14 and 11q22-23 in chronic lymphocytic leukemia

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BlankExpression 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.

T Herold, V Jurinovic, M Mulaw, T Seiler, A Dufour, S Schneider, PM Kakadia, M

Feuring-Buske, J Braess, K Spiekermann, U Mansmann, W Hiddemann, C Buske, and SK

Bohlander

Genes Chromosomes Cancer, April 15, 2011; .

Department of Medicine III, University Hospital Grosshadern,

Ludwig-Maximilians-University, and Clinical ative Group Leukemia,

Helmholtz Center Munich for Environmental Health, Munich, Germany.

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. ? 2011 Wiley-Liss, Inc.

PMID: 21500311