Frequent genomic imbalances suggest commonly altered tumour genes in humanhepatocarcinogenesis

Hepatocellular carcinoma (HCC) is one of the most frequent-occurring malign ant tumours worldwide, but molecular changes of tumour DNA, with the except ion of viral integrations and p53 mutations, are poorly understood. In orde r to search for common macro-imbalances of genomic tumour DNA, 21 HCCs and 3 HCC-cell lines were characterized by comparative genomic hybridization (C GH), subsequent database analyses and in selected cases by fluorescence in situ hybridization (FISH). Chromosomal subregions of 1q, 8q, 17q and 20q sh owed frequent gains of genomic material, while losses were most prevalent i n subregions of 4q, 6q, 13q and 16q. Deleted regions encompass tumour suppr essor genes, like RB-1 and the cadherin gene cluster, some of them previous ly identified as potential target genes in HCC development. Several potenti al growth- or transformation-promoting genes located in chromosomal subregi ons showed frequent gains of genomic material. The present study provides a basis for further genomic and expression analyses in HCCs and in addition suggests chromosome 4q to carry a so far unidentified tumour suppressor gen e relevant for HCC development. (C) 2001 Cancer Research Campaign.