No abstract

Tumors arising from the liver, biliary tract and pancreas, which originate in the foregut and are in close anatomical proximity to each other, sometimes show similar histological features. No studies have focused on genetic similarities and differences between tumors of these organs. To elucidate the similarities and differences in DNA copy number alterations between tumors of these organs, we applied comparative genomic hybridization (CGH) to cancers of the liver (31 cases), biliary tract (42 cases) and pancreas (27 cases). Some alterations were common to tumors of all three organs, and some were preferential in certain types of tumor. Gains of 1q and 8q and losses of 8p and 17p were common to all tumors. In contrast, 13q14 and 16q losses were detected exclusively in hepatocellular carcinomas (HCCs; p < 0.01). The incidence of 17q21 gain and 5q loss was higher in biliary tract cancers than in the other two types (p < 0.05). Pancreatic cancers exhibited higher incidence of 5q14-q23 gain and 19p loss than tumors of other organs (p < 0.01). Gains of 7p, 7q, 12p and 20q and losses of 3p, 6q, 9p and 18q were frequent in both biliary tract and pancreatic cancers but rare in HCCs (p < 0.05). The present results suggest that although genes located at 1q, 8p, 8q and 17p are frequently involved in HCC, biliary tract and pancreatic cancer, at least some of the genes implicated in carcinogenesis are different between these three types. It is also suggested that CGH analysis is useful as a potential adjunct for the diagnosis and management of these tumors of organs that are anatomically close to one another.

The presence of K‐ras gene mutation was examined in experimentally induced preneoplastic pancreatic ductal lesions. Syrian hamsters received 70 mg/kg of N‐nitrosobis(2‐oxopropyl)amine (BOP) followed by repeated exposure to an augmentation pressure regimen consisting of choline‐deficient diet combined with dl‐ethionine and l‐methionine and administration of 20 mg/kg BOP. After two augmentation pressure cycles, pancreatic ductal cell hyperplasias appeared and after three cycles, atypical hyperplasias of pancreatic ductal cells and intraductal carcinomas developed. K‐ras mutations were detected by single‐strand conformation polymorphism analysis of polymerase chain reaction products and nucleotide sequencing. The results showed that K‐ras mutation had occurred in one of 9 simple hyperplasias of pancreatic ductal epithelium, in 5 of 9 atypical hyperplasias, and in 4 of 8 intraductal carcinomas. The findings thus suggested that K‐ras is activated in association with very early stage malignant transformation of pancreatic ductal cells in hamsters.

The mechanism of transcriptional regulation of the H‐2Kbm1 major histocompatibility complex (MHC) class I gene by adenovirus type 12 E1A (Ad12‐E1A) was studied in transfected rat embryonal fibroblasts. Results of long‐term expression of the chloramphenicol acetyl transferase (CAT) gene placed under the control of the 5′‐flanking region of the mouse MHC class I gene. H‐2Kbm1, and the results of nuclear run‐on transcription assays, yield evidence for both positive and negative regulation of H‐2Kbm1 by E1A gene product. Deletion studies in the H‐2Kbm1 promoter region revealed that a proximal 58 bp upstream sequence (‐194 to ‐136, relative to the cap site) and a distal 316 bp sequence (‐1837 to ‐1521) respectively contribute to positive and negative regulation mediated by the E1A gene product. Both regulatory elements of MHC class I gene promoter region are responsible for the differential expression of the H‐2Kbm1 gene in Ad12 transformed cells. A nuclear factor binding to the negative element has been detected only in extracts derived from cells expressing Ad12‐E1A.