Trinucleotide repeat dynamic mutation identifying susceptibility in familial and sporadic chronic lymphocytic leukaemia
Rebecca L. Auer
Centre for Haematology, Institute of Cell and Molecular Science, Bart's & The London Queen Mary School of Medicine, London, UK
Search for more papers by this authorGuillaume Dighiero
Unite d'Immuno-hematologie et d'Immunopathologie, Institut Pasteur, Paris, France
Search for more papers by this authorLynn R. Goldin
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA
Search for more papers by this authorDenise Syndercombe-Court
Centre for Haematology, Institute of Cell and Molecular Science, Bart's & The London Queen Mary School of Medicine, London, UK
Search for more papers by this authorChristopher Jones
Centre for Haematology, Institute of Cell and Molecular Science, Bart's & The London Queen Mary School of Medicine, London, UK
Search for more papers by this authorSuzanne McElwaine
Centre for Haematology, Institute of Cell and Molecular Science, Bart's & The London Queen Mary School of Medicine, London, UK
Search for more papers by this authorAdrian C. Newland
Centre for Haematology, Institute of Cell and Molecular Science, Bart's & The London Queen Mary School of Medicine, London, UK
Search for more papers by this authorChristopher D. Fegan
Department of Haematology, Cardiff and Vale NHS Trust, Cardiff, UK
Search for more papers by this authorNeil Caporaso
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA
Search for more papers by this authorFinbarr E. Cotter
Centre for Haematology, Institute of Cell and Molecular Science, Bart's & The London Queen Mary School of Medicine, London, UK
Search for more papers by this authorRebecca L. Auer
Centre for Haematology, Institute of Cell and Molecular Science, Bart's & The London Queen Mary School of Medicine, London, UK
Search for more papers by this authorGuillaume Dighiero
Unite d'Immuno-hematologie et d'Immunopathologie, Institut Pasteur, Paris, France
Search for more papers by this authorLynn R. Goldin
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA
Search for more papers by this authorDenise Syndercombe-Court
Centre for Haematology, Institute of Cell and Molecular Science, Bart's & The London Queen Mary School of Medicine, London, UK
Search for more papers by this authorChristopher Jones
Centre for Haematology, Institute of Cell and Molecular Science, Bart's & The London Queen Mary School of Medicine, London, UK
Search for more papers by this authorSuzanne McElwaine
Centre for Haematology, Institute of Cell and Molecular Science, Bart's & The London Queen Mary School of Medicine, London, UK
Search for more papers by this authorAdrian C. Newland
Centre for Haematology, Institute of Cell and Molecular Science, Bart's & The London Queen Mary School of Medicine, London, UK
Search for more papers by this authorChristopher D. Fegan
Department of Haematology, Cardiff and Vale NHS Trust, Cardiff, UK
Search for more papers by this authorNeil Caporaso
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA
Search for more papers by this authorFinbarr E. Cotter
Centre for Haematology, Institute of Cell and Molecular Science, Bart's & The London Queen Mary School of Medicine, London, UK
Search for more papers by this authorSummary
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.
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