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Br J Haematol. 2010 Nov;151(4):336-45. doi: 10.1111/j.1365-2141.2010.08341.x. Epub 2010 Aug 31.

Comparison of familial and sporadic chronic lymphocytic leukaemia using high resolution array comparative genomic hybridization.

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1
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

Approximately 10% of patients with chronic lymphocytic leukaemia (CLL) have a family history of the disease or a related lymphoproliferative disorder, yet the relationship of familial CLL to genomic abnormalities has not been characterized in detail. We therefore studied 75 CLL patients, half familial and half sporadic, using high-resolution array comparative genomic hybridization (CGH), in order to better define the relationship of genomic abnormalities to familial disease and other biological prognostic factors. Our results showed that the most common high-risk deletion in CLL, deletion 11q, was significantly associated with sporadic disease. Comparison of familial to sporadic disease additionally identified a copy number variant region near the centromere on 14q, proximal to IGH@, in which gains were associated both with familial CLL, and with mutated IGHV and homozygous deletion of 13q. Homozygous deletion of 13q was also found to be associated with mutated IGHV and low expression of ZAP-70, and a significantly longer time to first treatment compared to heterozygous deletion or lack of alteration. This study is the first high resolution effort to investigate and report somatic genetic differences between familial and sporadic CLL.

PMID:
20812997
PMCID:
PMC3584328
DOI:
10.1111/j.1365-2141.2010.08341.x
[Indexed for MEDLINE]
Free PMC Article
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