Comparison of familial and sporadic chronic lymphocytic leukaemia using high resolution array comparative genomic hybridization.
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.
Setlur
Sunita R
SR
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Ihm
Chunhwa
C
Tchinda
Joelle
J
Shams
Soheil
S
Werner
Lillian
L
Cho
Eun Kyung
EK
Thompson
Christina
C
Phillips
Kimberly
K
Rassenti
Laura Z
LZ
Kipps
Thomas J
TJ
Neuberg
Donna
D
Freedman
Arnold S
AS
Lee
Charles
C
Brown
Jennifer R
JR
D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged
Lancet. 1999 Jan 2;353(9146):26-9
10023947
Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13944-9
16166262
Leukemia. 2002 Jul;16(7):1229-32
12094247
Cancer Invest. 1992;10(2):103-9
1551021
Cytogenet Genome Res. 2007;118(1):8-12
17901694
Blood. 1996 Jun 15;87(12):4990-7
8652811
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15524-9
12434020
Genes Chromosomes Cancer. 2008 Aug;47(8):697-711
18484635
N Engl J Med. 2004 Aug 26;351(9):893-901
15329427
Nature. 2006 Nov 23;444(7118):444-54
17122850
Blood. 2009 Feb 5;113(6):1294-303
18922857
N Engl J Med. 2000 Dec 28;343(26):1910-6
11136261
Haematologica. 2006 Aug;91(8):1117-20
16885053
Br J Haematol. 2000 Jun;109(4):794-9
10929032
N Engl J Med. 1990 Sep 13;323(11):720-4
2201915
Leuk Res. 2010 Jan;34(1):63-8
19406473
Br J Haematol. 2008 Nov;143(4):532-6
18752589
Leuk Lymphoma. 2008 Oct;49(10):1879-86
18949611
Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5413-7
2052620
Br J Haematol. 1996 Feb;92(2):382-8
8603004
Leuk Res. 1997 Nov-Dec;21(11-12):1011-23
9444933
Leuk Lymphoma. 2001 Jun;42(1-2):99-108
11699227
Leukemia. 1997 Nov;11(11):1929-32
9369428
Blood. 2008 Sep 1;112(5):1993-2003
18436738
Genome Res. 2006 Sep;16(9):1149-58
16899652
Leukemia. 1992 Apr;6(4):246-50
1588788
Blood. 2007 Feb 1;109(3):1202-10
17053054
Br J Haematol. 2008 Nov;143(3):361-8
18729853
J Mol Diagn. 2008 Sep;10(5):442-51
18687794
Blood. 1998 Feb 15;91(4):1382-90
9454769
Leukemia. 1995 Dec;9(12):2003-8
8609709
Am J Hematol. 2008 Jul;83(7):540-6
18161787
Leukemia. 2010 Jan;24(1):211-5
19741724