Inactivation of the hypermethylated in cancer 1 tumour suppressor--not just a question of promoter hypermethylation?

Jenal, Mathias; Britschgi, Christian; Fey, Martin F; Tschan, Mario P (2010). Inactivation of the hypermethylated in cancer 1 tumour suppressor--not just a question of promoter hypermethylation? Swiss medical weekly, 140, w13106. Muttenz: EMH Schweizerischer Ärzteverlag 10.4414/smw.2011.13106

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The chromosomal region 17p13.3 is frequently deleted or epigenetically silenced in a variety of human cancers. It includes the hypermethylated in cancer 1 (HIC1) 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, HIC1 functionally cooperates with p53 to suppress cancer development. 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 hypermethylated in cancer 1 (HIC1). Further, it was shown that in the majority of cases hypermethylation of this chromosomal region leads to epigenetic inactivation of HIC1. A role for HIC1 in tumour development is further supported by a mouse model, since various spontaneous, age- and gender-specific malignant tumours occur in heterozygous Hic1+/- knockout mice. Furthermore, exogenously delivered HIC1 leads to a significant decrease in clonogenic survival in cancer cell lines. This review highlights the role of HIC1 inactivation in solid tumours and particularly in leukaemia development.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Britschgi, Christian; Fey, Martin and Tschan, Mario

ISSN:

1424-7860

Publisher:

EMH Schweizerischer Ärzteverlag

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:09

Last Modified:

06 Dec 2013 13:20

Publisher DOI:

10.4414/smw.2011.13106

PubMed ID:

21104471

Web of Science ID:

000287646100006

URI:

https://boris.unibe.ch/id/eprint/1073 (FactScience: 201820)

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