Trinucleotide repeat dynamic mutation identifying susceptibility in familial and sporadic chronic lymphocytic leukaemia.
Chronic lymphocytic leukaemia (CLL) has a strong hereditary component, but an understanding of predisposition genes is poor. Anticipation with familial CLL has been reported, although the molecular mechanism is unknown. Expansion of trinucleotide repeat sequences underlies anticipation observed in neurodegenerative disease. A polymerase chain reaction-based assay was used to analyse the stability of ten CCG- and CAG-trinucleotide repeat tracts in 18 CLL families and 140 patients with the sporadic form of the disease. The study suggests that anticipation, if it occurs in CLL, is not linked to CCG- and CAG-repeat expansion, however, variation in repeat length at certain loci (FRA16A) may permit identification of susceptible family members. In addition, polymorphisms with prognostic significance were identified. These were high length (but not expanded) repeats at FRA11B (P = 0.01), ATXN1 (P = 0.032) and ATXN3 (P = 0.022), all associated with poor risk disease.
Auer
Rebecca L
RL
Centre for Haematology, Institute of Cell and Molecular Science, Bart's and The London Queen Mary School of Medicine, London, UK.
Dighiero
Guillaume
G
Goldin
Lynn R
LR
Syndercombe-Court
Denise
D
Jones
Christopher
C
McElwaine
Suzanne
S
Newland
Adrian C
AC
Fegan
Christopher D
CD
Caporaso
Neil
N
Cotter
Finbarr E
FE
D017668:Age of Onset; D000704:Analysis of Variance; D020132:Anticipation, Genetic; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D018709:Statistics, Nonparametric; D018911:Trinucleotide Repeats