Genomic analysis of scirrhous gastric cancer in a young adult

H Mita MD PhD, F Itoh MD PhD, M Toyota MD PhD, and K Imai MD PhD

First Department of Internal Medicine, Sapporo Medical University, School of Medicine, Sapporo, Hokkaido Japan

AIMS: Analysis of the scirrhous gastric cancer of a young adult. (1) To detect previously unidentified genetic alterations in a scirrhous gastric cancer of a young adult using an improved method of representational difference analysis (RDA) (Efficiency-monitored RDA (EM-RDA) which monitors the efficiency of genomic subtraction. (2) To investigate the role of aberrant methylation in scirrhous gastric cancer in the young adult. METHODS: (1) Genomic DNA was extracted from frozen sections of the gastric cancer of a 24 year old woman. EM-RDA was performed using cancer DNA as a tester and corresponding normal DNA as a driver while monitoring the efficiency of subtraction. Epstein-Barr virus (EBV) RNA in situ hybridization studies in formalin-fixed paraffin-embedded carcinoma tissues sections were performed using the EBV-encoded small RNA 1 (EBER1) gene. (2)The methylation status of 7 CpG islands including p16 were analyzed by bisulfite-PCR using Na-bisulfite treated genomic DNA. RESULTS: Two DNA fragments of the EBV genome were detected in the scirrhous cancer by EM-RDA. Positive EBER1 signals were observed in the nuclei of carcinoma but not in normal lymphoid cells. Simultaneous methylation of 6 loci including p16 was observed in the gastric cancer genomic DNA. CONCLUSIONS: The scirrhous gastric cancer in the young adult was characterized as an EBV-related gastric cancer by EM-RDA and it showed a hypermethylator phenotype. This suggests that EBV might be involved both in the tumorigenesis of gastric cancer of young adults and in hyper-methylation of CpG islands.

KEY WORDS: poorly differentiated adenocarcinoma, diffuse, infiltrative.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Predictive Markers.