PMID- 17047154
OWN - NLM
STAT- MEDLINE
DCOM- 20070306
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 109
IP  - 3
DP  - 2007 Feb 1
TI  - Identification of a novel chromosome region, 13q21.33-q22.2, for susceptibility 
      genes in familial chronic lymphocytic leukemia.
PG  - 916-25
AB  - Chronic lymphocytic leukemia (CLL) is the most prevalent form of leukemia in 
      adults in western countries. A genome scan of CLL-prone families revealed a lod 
      score of one in band 13q22.1. To investigate this finding, we selected 6 CLL 
      families consisting of 63 individuals (CLL affected, n=19; unaffected, n=44) for 
      fine mapping of a 23-megabase region in 13q14.2-q22.2. Interphase fluorescence in 
      situ hybridization (FISH) revealed 13q14 deletion in 85% (11/13) of CLL patients. 
      Four CLL families shared a 3.68-Mb minimal region in 13q21.33-q22.2. Two 
      asymptomatic siblings who shared the 13q21.33-q22.2 at-risk haplotype exhibited 
      CD5+ monoclonal B-cell lymphocytosis (MBL) on flow cytometry. One of these 
      individuals also had a 13q14 deletion by FISH. These 2 individuals with MBL 
      shared the at-risk haplotype with their CLL-affected relatives, providing further 
      evidence of the relationship between CLL and MBL, as well as of the biologic 
      significance of this novel region. Using direct DNA sequencing analysis, we 
      screened 13 genes for mutations, but no frameshift or nonsense mutations were 
      detected. Our studies revealed that 11 of the 13 genes in the candidate region 
      were expressed in immune tissues, supporting their functional relevance in 
      investigations of familial CLL. In conclusion, we identified a novel candidate 
      region that may predispose to familial CLL.
FAU - Ng, David
AU  - Ng D
AD  - Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, 
      National Cancer Institute, National Institutes of Health, Department of Health 
      and Human Services, Rockville, MD 20892-7231, USA.
FAU - Toure, Ousmane
AU  - Toure O
FAU - Wei, Ming-Hui
AU  - Wei MH
FAU - Arthur, Diane C
AU  - Arthur DC
FAU - Abbasi, Fatima
AU  - Abbasi F
FAU - Fontaine, Laura
AU  - Fontaine L
FAU - Marti, Gerald E
AU  - Marti GE
FAU - Fraumeni, Joseph F Jr
AU  - Fraumeni JF Jr
FAU - Goldin, Lynn R
AU  - Goldin LR
FAU - Caporaso, Neil
AU  - Caporaso N
FAU - Toro, Jorge R
AU  - Toro JR
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20061017
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
SB  - IM
MH  - Adult
MH  - Aged
MH  - B-Lymphocytes
MH  - Chromosome Aberrations
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 13
MH  - DNA Mutational Analysis
MH  - Family Health
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Genomics
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*genetics
MH  - Lod Score
MH  - Lymphocytosis/genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Pedigree
EDAT- 2006/10/19 09:00
MHDA- 2007/03/07 09:00
CRDT- 2006/10/19 09:00
PHST- 2006/10/19 09:00 [pubmed]
PHST- 2007/03/07 09:00 [medline]
PHST- 2006/10/19 09:00 [entrez]
AID - S0006-4971(20)51973-3 [pii]
AID - 10.1182/blood-2006-03-011825 [doi]
PST - ppublish
SO  - Blood. 2007 Feb 1;109(3):916-25. doi: 10.1182/blood-2006-03-011825. Epub 2006 Oct 
      17.