title: p53 intronic point mutation, aberrant splicing and telomeric associations in a case of B-chronic lymphocytic leukaemia.
abstract: We report a case of chronic lymphocytic leukaemia (CLL) with telomeric associations and a p53 intronic point mutation. Karyotypic analysis revealed clonal and non-clonal telomeric associations, accompanied by clonal cytogenetic abnormalities and also in isolation. The p53 mutation, which occurred at the invariant base pair -2 of the splice acceptor site in intron 7 resulted in the abolition of correct splicing of exon 7 to exon 8. Multiple aberrant splice products were characterized, all of which differed from wildtype in the DNA binding domain. Fluorescence in situ hybridization demonstrated that the clone retained two copies of the p53 gene and wild-type p53 transcript was detected on cloning of reverse transcriptase polymerase chain reaction (RT-PCR) product, indicating that one wild-type allele remained. However, a plasmid clone with correct splicing at the exon 7/8 boundary, but with a 21 bp deletion in exon 8, was also found at low frequency. This finding indicates clonal evolution, resulting in complete loss of wild-type p53. The intronic point mutation was not present in DNA extracted from cervical tissue indicating that it was a leukaemic phenomenon. This is the first case of an intronic point mutation to be reported in CLL. This mutation led to chaotic p53 expression and, interestingly, occurred in a case showing telomeric associations, a rare phenomenon in B-CLL.
authors.affiliation: Leukaemia Research Unit, Taunton and Somerset Hospital, UK. teresa.bromidge@tauntonsom-tr.swest.nhs.uk
authors.forename: T
authors.initials: T
authors.lastname: Bromidge
authors.forename: C
authors.initials: C
authors.lastname: Lowe
authors.forename: A
authors.initials: A
authors.lastname: Prentice
authors.forename: S
authors.initials: S
authors.lastname: Johnson
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000235:genetics; D002881:Chromosomes, Human, Pair 12; D002889:Chromosomes, Human, Pair 2; D002899:Chromosomes, Human, Pair 9; D005260:Female; D016158:Genes, p53; D006801:Humans; D007438:Introns; D007621:Karyotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000235:genetics*; D008048:Lip Neoplasms / Q000150:complications / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D009378:Neoplasms, Multiple Primary / Q000235:genetics; D017354:Point Mutation; D022821:RNA Splice Sites; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016615:Telomere; D014314:Trisomy; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000235:genetics
chemical_list: D022821:RNA Splice Sites