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The worldwide incidence of hepatocellular carcinoma (HCC) is approximately one million cases a year. This makes HCC one of the most frequent human malignancies, especially in Asia and Africa, although the incidence is increasing also in the western world. HCC is a complication of chronic liver disease, with cirrhosis as the most important risk factor. Viral co-pathogenesis makes cirrhosis due to hepatitis B (HBV) and hepatitis C virus (HCV) infection a very important factor in the development of HCC. As curative therapy is often ruled out due to the late detection of HCC, it would be attractive to find parameters which predict malignant transformation in HBV- and HCV-infected livers. This study has used comparative genomic hybridization (CGH) to analyse 26 HCCs (11 non-viral, nine HBV, six HCV) and 12 concurrent dysplasias (five non-viral, five HBV, two HCV). Frequent gain (≥25% of all tumours) was detected, in decreasing order of frequency, on 8q (69%), 1q (46%), 17q (46%), 12q (42%), 20q (31%), 5p (27%), 6q (27%), and Xq (27%). Frequent loss (≥25% of all tumours) was found, in decreasing order of frequency, on 8p (58%), 16q (54%), 4q (42%), 13q (39%), 1p (35%), 4p (35%), 16p (35%), 18q (35%), 14q (31%), 17p (31%), 9p (27%), and 9q (27%). Minimal overlapping regions could be determined at multiple locations (candidate genes in parentheses). Minimal regions of overlap for deletions were assigned to 4p14–15 (PCDH7), 8p21–22 (FEZ1), 9p12–13, 13q14–31 (RB1), 14q31 (TSHR), 16p12–13.1 (GSPT1), 16q21–23 (CDH1), 17p12–13 (TP53), and 18q21–22 (DPC4, DCC). Minimal overlapping amplified sites could be seen at 8q24 (MYC), 12q15–21 (MDM2), 17q22–25 (SSTR2, GH1), and 20q12–13.2 (MYBL2, PTPN1). A single high level amplification was seen on 5q21 in an HBV-related tumour. Aberrations appeared more frequent in HBV-related HCCs than in HCV-associated tumours (p=0.008). This was most prominent with respect to losses (p=0.004), specifically loss on 4p (p=0.007), 16q (p=0.04), 17p (p=0.04), and 18q (p=0.03). In addition, loss on 17p was significantly lower in non-viral cancers than in HBV-related HCC (p<0.001). Furthermore, loss on 13q was more prevalent in HCCs in non-cirrhotic livers (p=0.02), thus suggesting a different, potentially more aggressive, pathway in neoplastic progression. A tendency (p=0.07) was observed for loss on 9q in high-stage tumours; no specific changes were found in relation to tumour grade. A subset of the HCC-associated genetic changes was disclosed in the preneoplastic stage, i.e. liver cell dysplasia. This group of dysplasias showed frequent gain on 17q (25%) and frequent loss on 16q (33%), 4q (25%), and 17p (25%). The majority of the dysplasias with alterations revealed genetic changes that were also present in the primary tumour. In conclusion, firstly, this study has provided a detailed map of genomic changes occurring in HCC of viral and non-viral origin, and has suggested candidate genes. Loss on 17p, including the TP53 region, appeared significantly more prevalent in HBV-associated liver cancers, whereas loss on 13q, with possible involvement of RB1, was distinguished as a possible genetic biomarker. Secondly, CGH analysis of liver cell dysplasia, both viral and non-viral, has revealed HCC-specific early genetic changes, thereby confirming its preneoplastic nature. Finally, genes residing in these early altered regions, such as CDH1 or TP53, might be associated with hepatocellular carcinogenesis. Copyright © 2000 John Wiley & Sons, Ltd. List of abbreviations: protocadherin 7 (PCDH7); F37 oesophageal cancer-related leucine-zipper motif (FEZ1); v-myc oncogene (MYC); mouse double minute 2 (p53 binding protein) (MDM2); retinoblastoma 1 (RB1); thyroid stimulating hormone receptor (TSHR); G1 to S-phase transition 1 (GSPT1); cadherin 1 (E-cadherin) (CDH1); tumour protein p53 (TP53); somatostatin receptor 2 (SSTR2); growth hormone 1 (GH1); deleted in pancreatic carcinoma (DPC4); deleted in colorectal carcinoma (DCC); v-myb myeloblastosis-like oncogene 2 (MYBL2); protein tyrosine phosphatase non-receptor type 1 (PTPN1).

Oesophageal adenocarcinomas arising in Barrett's epithelium occasionally present as multiple lesions. This could be due to either a multifocal presentation of the same tumour, or different neoplasms arising simultaneously in a dysplastic Barrett's oesophagus (‘field cancerization’). This is a report of the genetic analysis of multiple neoplastic sites in a Barrett's oesophagus with an extensive area of dysplasia. In addition, the dysplastic Barrett's epithelium was evaluated. For the genetic screening, comparative genomic hybridization (CGH) allowed evaluation of the whole genome of each specimen. Five cancerous regions were selected and subsequently dissected from paraffin-embedded tissue blocks. The use of archival materials enabled a targeted collection of representative tumour locations. Multiple genetic aberrations were detected by CGH in all cancer sites. Losses on 3p, 4, 7q, 18q, and Y, as well as gains on 8q, 9q, 12p, 13q, 17q, 20p and X, were found in each specimen. In four out of the five lesions, simultaneous losses on 9p, 15q, and 16q, with concomitant gains on 5p, 7q, and 10p, were disclosed by CGH. Adjacent high-grade dysplastic Barrett's mucosa shared the losses on 3p, 4, 7q, 9p, 18, and Y, as well as the gains on 5p, 7q, 13q, 17q, and X, thereby confirming its precursor status. Within this single and rare case of multifocal Barrett's adenocarcinoma, a monoclonal genotype was present. This must have been caused by an extensive outgrowth of a single tumour. Copyright © 1999 John Wiley & Sons, Ltd.

In an attempt to identify C/EBP-like transcription factors expressed in the prostate, a cDNA homologous to the mouse C/EBPδ (CRP3) and the rat CELF gene was isolated. A genomic clone containing the entire C/EBPδ gene was isolated using a cDNA fragment as a probe. The gene was characterized by restriction mapping and sequence analysis. By fluorescence in situ hybridization, using tile biotinylated genomic clone as a probe, the C/EBPδ gene was assigned to the pericentromeric region of human chromosome 8, most probably to 8q11. This chromosomal localization was confirmed by analysis of a panel of human x hamster somatic cell hybrid DNA samples with a C/EBPδ-specific STS. As a result, the C/EBPδ gene could be positioned between the PLAT and the MOS loci. Copyright 1993, 1999 Academic Press