Cancer-specific region of hypermethylation identified within the HIC1 putative tumour suppressor gene in acute myeloid leukaemia

Abnormal DNA methylation has been found to be a common feature in cancer ce lls, although the mechanism of this alteration remains poorly understood. H IC1 is a putative tumour suppressor gene on chromosome 17p13.3 and is hyper methylated in a number of cancers including leukaemia. In this study, using bisulphite genomic sequencing, we have identified a 'boundary' sequence wi thin the HIC1 CpG island that shows a marked junction between methylated an d unmethylated DNA in normal haematopoietic cells. Surprisingly, this bound ary of differential methylation lies exactly between the intron 2 and exon 3 junction. In contrast to normal haematopoietic cells, hypermethylation ex tends past this boundary at a high frequency (83%) in newly diagnosed acute myeloid leukaemias (AML). Identification of the hypermethylated boundary s equence not only provides the first step in understanding the mechanisms th at normally protect CpG islands from de novo methylation but also may prove to be a useful cancer-specific marker.