Data from The Prognostic Significance of Various 13q14 Deletions in Chronic Lymphocytic Leukemia

Abstract

<div>Abstract<p><b>Purpose:</b> To further our understanding of the biology and prognostic significance of various chromosomal 13q14 deletions in chronic lymphocytic leukemia (CLL).</p><p><b>Experimental Design:</b> We analyzed data from SNP 6.0 arrays to define the anatomy of various 13q14 deletions in a cohort of 255 CLL patients and have correlated two subsets of 13q14 deletions (type I exclusive of <i>RB1</i> and type II inclusive of <i>RB1</i>) with patient survival. Furthermore, we measured the expression of the 13q14-resident microRNAs by quantitative PCR (Q-PCR) in 242 CLL patients and subsequently assessed their prognostic significance. We sequenced all coding exons of <i>RB1</i> in patients with monoallelic <i>RB1</i> deletion and have sequenced the 13q14-resident <i>miR</i> locus in all patients.</p><p><b>Results:</b> Large 13q14 (type II) deletions were detected in approximately 20% of all CLL patients and were associated with shortened survival. A strong association between 13q14 type II deletions and elevated genomic complexity, as measured through CLL-FISH or SNP 6.0 array profiling, was identified, suggesting that these lesions may contribute to CLL disease evolution through genomic destabilization. Sequence and copy number analysis of the <i>RB1</i> gene identified a small CLL subset that is <i>RB1</i> null. Finally, neither the expression levels of the 13q14-resident microRNAs nor the degree of 13q14 deletion, as measured through SNP 6.0 array-based copy number analysis, had significant prognostic importance.</p><p><b>Conclusions:</b> Our data suggest that the clinical course of CLL is accelerated in patients with large (type II) 13q14 deletions that span the <i>RB1</i> gene, therefore justifying routine identification of 13q14 subtypes in CLL management. <i>Clin Cancer Res; 17(21); 6778–90. ©2011 AACR</i>.</p></div>