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 cells, although the mechanism of this alteration remains poorly understood. HIC1 is a putative tumour suppressor gene on chromosome 17p13.3 and is hypermethylated in a number of cancers including leukaemia. In this study, using bisulphite genomic sequencing, we have identified a 'boundary' sequence within the HIC1 CpG island that shows a marked junction between methylated and unmethylated DNA in normal haematopoietic cells. Surprisingly, this boundary of differential methylation lies exactly between the intron 2 and exon 3 junction. In contrast to normal haematopoietic cells, hypermethylation extends past this boundary at a high frequency (83%) in newly diagnosed acute myeloid leukaemias (AML). Identification of the hypermethylated boundary sequence not only provides the first step in understanding the mechanisms that normally protect CpG islands from de novo methylation but also may prove to be a useful cancer-specific marker.
Melki
J R
JR
Kanematsu Laboratories, Royal Prince Alfred Hospital, Camperdown, NSW Australia.
Vincent
P C
PC
Clark
S J
SJ
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001483:Base Sequence; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D014157:Transcription Factors / Q000235:genetics*
D004273:DNA, Neoplasm; C096870:Hic1 protein, mouse; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors