Showing papers by "Brian J. P. Huntly published in 2001"
TL;DR: The results indicate that deletions occur at the time of the Philadelphia (Ph) translocation and may result in considerable genetic heterogeneity ab initio, a concept that is likely to apply to other malignancies associated with translocations.
256 citations
TL;DR: The standard Philadelphia (Ph) translocation t(9;22), its variants and a proportion of Ph-negative cases are positive for the BCR-ABL fusion gene, as determined by molecular analysis.
44 citations
TL;DR: This work reveals hidden variant Philadelphia translocations in two cases of Ph‐positive chronic‐phase chronic myeloid leukaemia and illustrates that even established cytogenetic abnormalities may contain cryptic abnormalities beyond the resolution of conventional cytogenetics methods.
Abstract: A range of fluorescent in situ hybridization techniques have been used to reveal hidden variant Philadelphia translocations in two cases of Ph-positive chronic-phase chronic myeloid leukaemia. In one patient, a highly complex variant Ph translocation affecting four chromosomes had resulted in the formation of structures with the appearance of i(17q) and +8. Misinterpretation of these karyotypes has direct clinical relevance. Our findings illustrate that even established cytogenetic abnormalities may contain cryptic abnormalities beyond the resolution of conventional cytogenetic methods.
14 citations
TL;DR: It is demonstrated that neither mutation nor abnormal methylation of the TGF‐β RII gene is associated with the pathogenesis of PV and a novel method, termed methylation‐specific strand extension (MSSE), for the detection of methylated CpG dinucleotides is presented.
Abstract: Polycythaemia vera (PV) is a myeloproliferative disorder (MPD) thought to result from transformation of a haemopoietic stem cell. Transforming growth factor beta1 (TGF-beta1) is a negative regulator of haemopoietic stem cells, an effect mediated by direct binding to TGF-beta receptor II (TGF-beta RII). Reduced levels of TGF-beta RII mRNA or protein have been reported in several MPDs including PV, suggesting a role for TGF-beta RII in PV. No mutational analysis of the TGF-beta RII gene has yet been performed in PV. To investigate whether genetic or epigenetic alteration of the TGF-beta RII gene contributes to the pathogenesis of PV, we performed mutation and methylation analysis in 15 PV patients. The promoter, all seven exons and all intron/exon junctions were studied using single-strand conformation polymorphism (SSCP) and heteroduplex analysis (HA). In total, three single nucleotide polymorphisms (SNPs) were identified. These were located in the promoter, intron 2 and exon 5. No acquired mutations were detected in any patient sample. We also present a novel method, termed methylation-specific strand extension (MSSE), for the detection of methylated CpG dinucleotides. The combination of bisulphite modification and MSSE permits rapid analysis of the methylation status of CpG dinucleotides in multiple samples. We analysed the methylation status of the promoter and of a CpG island within exon 1 in 15 PV patients. No aberrant methylation was detected in either of these regions. These data demonstrate that neither mutation nor abnormal methylation of the TGF-beta RII gene is associated with the pathogenesis of PV. Furthermore, MSSE is a rapid and robust approach for assessing the methylation status of a given genomic region.
13 citations