title: Identification of a novel chromosome region, 13q21.33-q22.2, for susceptibility genes in familial chronic lymphocytic leukemia.
abstract: 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.
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Ng
authors.forename: Ousmane
authors.initials: O
authors.lastname: Toure
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Wei
authors.forename: Diane C
authors.initials: DC
authors.lastname: Arthur
authors.forename: Fatima
authors.initials: F
authors.lastname: Abbasi
authors.forename: Laura
authors.initials: L
authors.lastname: Fontaine
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Marti
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Fraumeni
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Goldin
authors.forename: Neil
authors.initials: N
authors.lastname: Caporaso
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Toro
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008126:Lod Score; D008218:Lymphocytosis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010375:Pedigree