Nature Genetics
1, 570 - 577 (1995)
doi:10.1038/nm0695-570
p53 activates expression of HIC-1, a new candidate tumour suppressor gene on 17p13.3Michele Makos Wales1, Margaret A. Biel1, Wafik El Deiry2, 3, Barry D. Nelkin2, Jean-Pierre Issa2, Webster K. Cavenee4, Steven J. Kuerbitz2, 5
& Stephen B. Baylin1, 2, 6, 7
1Human Genetics Graduate Program, 424 North Bond Street, Baltimore, Maryland 21231, USA
2The Oncology Center, the Johns Hopkins Medical Institutions, 424 North Bond Street, Baltimore, Maryland 21231, USA
3Present address: Hematology-Oncology Division, University of Pennsylvania School of Medicine, 36th and Hamilton Walk, Philadelphia, Pennsylvania 19104, USA
4The Ludwig Cancer Institute for Cancer Research and Department of Medicine and Center for Molecular Genetics, University of California at San Diego, La Jolla, California 92093, USA
5Department of Pediatrics, the Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
6Department of Medicine, the Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
7Correspondence should be addressed to S.B.B. at Johns Hopkins Oncology Center. For several human tumour types, allelic toss data suggest that one or more tumour suppressor genes reside telomeric to the p53 gene at chromosome 17p13.1. In the present study we have used a new strategy, involving molecular analysis of a DNA site hypermethylated in tumour DNA, to identify a candidate gene in this region (17p13.3). Our approach has led to identification of HIC-1 (hypermethylated in cancer), a new zinc-finger transcription factor gene which is ubiquitously expressed in normal tissues, but underexpressed in different tumour cells where it is hypermethylated. Multiple characteristics of this gene, including the presence of a p53 binding site in the 5' flanking region, activation of the gene by expression of a wild-type p53 gene and suppression of C418 selectability of cultured brain, breast and colon cancer cells following insertion of the gene, make HIC-1 gene a strong candidate for a tumour suppressor gene in region 17p13.3.
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