Abstract
<div>Abstract<p><b>Purpose:</b> The disease course of chronic lymphocytic leukemia (CLL) varies significantly within cytogenetic groups. We hypothesized that high-resolution genomic analysis of CLL would identify additional recurrent abnormalities associated with short time-to-first therapy (TTFT).</p><p><b>Experimental Design:</b> We undertook high-resolution genomic analysis of 161 prospectively enrolled CLLs using Affymetrix 6.0 SNP arrays, and integrated analysis of this data set with gene expression profiles.</p><p><b>Results:</b> Copy number analysis (CNA) of nonprogressive CLL reveals a stable genotype, with a median of only 1 somatic CNA per sample. Progressive CLL with 13q deletion was associated with additional somatic CNAs, and a greater number of CNAs was predictive of TTFT. We identified other recurrent CNAs associated with short TTFT: 8q24 amplification focused on the cancer susceptibility locus near <i>MYC</i> in 3.7%; 3q26 amplifications focused on <i>PIK3CA</i> in 5.6%; and 8p deletions in 5% of patients. Sequencing of <i>MYC</i> further identified somatic mutations in two CLLs. We determined which catalytic subunits of phosphoinositide 3-kinase (PI3K) were in active complex with the p85 regulatory subunit and showed enrichment for the α subunit in three CLLs carrying <i>PIK3CA</i> amplification.</p><p><b>Conclusions:</b> Our findings implicate amplifications of 3q26 focused on <i>PIK3CA</i> and 8q24 focused on <i>MYC</i> in CLL. <i>Clin Cancer Res; 18(14); 3791–802. ©2012 AACR</i>.</p></div>
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
