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Clin Cancer Res. 2012 Jul 15;18(14):3791-802. doi: 10.1158/1078-0432.CCR-11-2342. Epub 2012 May 23.

Integrative genomic analysis implicates gain of PIK3CA at 3q26 and MYC at 8q24 in chronic lymphocytic leukemia.

Author information

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Jennifer_Brown@dfci.harvard.edu

Abstract

PURPOSE:

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).

EXPERIMENTAL DESIGN:

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.

RESULTS:

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 MYC in 3.7%; 3q26 amplifications focused on PIK3CA in 5.6%; and 8p deletions in 5% of patients. Sequencing of MYC 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 PIK3CA amplification.

CONCLUSIONS:

Our findings implicate amplifications of 3q26 focused on PIK3CA and 8q24 focused on MYC in CLL.

PMID:
22623730
[PubMed - indexed for MEDLINE]
PMCID:
PMC3719990
Free PMC Article
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