TY - JOUR AU - Jenal, M AU - Britschgi, C AU - Fey, MF AU - Tschan, MP PY - 2010/10/25 Y2 - 2024/03/29 TI - Inactivation of the hypermethylated in cancer 1 tumour suppressor – not just a question of promoter hypermethylation? JF - Swiss Medical Weekly JA - Swiss Med Wkly VL - 140 IS - 4344 SE - Review article: Biomedical intelligence DO - 10.4414/smw.2010.13106 UR - https://smw.ch/index.php/smw/article/view/1208 SP - w13106 AB - <p><p>The chromosomal region 17p13.3 is frequently deleted or epigenetically silenced in a variety of human cancers. It includes the <em>hypermethylated in cancer 1 (HIC1)</em> gene placed telomerically to the p53 tumour suppressor gene. HIC1 encodes a transcriptional repressor, and its targets identified to date are genes involved in proliferation, tumour growth and angiogenesis. In addition, <em>HIC1</em> functionally cooperates with p53 to suppress cancer development.</p> <p>Frequent allelic loss at position 17p13.1 in human cancers often points to mutations of the tumour suppressor p53. However, in a variety of cancer types, allelic loss of the short arm of chromosome 17 may hit regions distal to p53 and, interestingly, without leading to p53 mutations. Furthermore, the neighbouring region 17p13.3 often shows loss of heterozygosity or DNA hypermethylation in various types of solid tumours and leukaemias. In line with this concept, Wales et al. described a new potential tumour suppressor in this region and named it <em>hypermethylated in cancer 1 (HIC1).</em> Further, it was shown that in the majority of cases hypermethylation of this chromosomal region leads to epigenetic inactivation of <em>HIC1.</em></p> <p>A role for <em>HIC1</em> in tumour development is further supported by a mouse model, since various spontaneous, age- and gender-specific malignant tumours occur in heterozygous <em>Hic1</em><sup>+/–</sup> knockout mice. Furthermore, exogenously delivered <em>HIC1</em>leads to a significant decrease in clonogenic survival in cancer cell lines. This review highlights the role of <em>HIC1</em> inactivation in solid tumours and particularly in leukaemia development.</p></p> ER -