A Comparison of DNA Copy Number Changes Detected by Comparative Genomic Hybridization in Malignancies of the Liver, Biliary Tract and Pancreas

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.

Genetic aberrations detected by comparative genomic hybridisation in vulvar cancers

“…The smallest area of gain was 8q21, which is centromeric to the location of the proto-oncogene MYC. Gain of 8q, including the 8q21 region, has been previously documented in many different cancer types, the majority of which are not related to HPV infection (Kallioniemi et al, 1994;Prat et al, 2001;Shiraishi et al, 2001;van Dekken et al, 2001). The current and other studies therefore support the notion that 8q houses important oncogene(s) other than MYC.…”

Telomere length variation in biliary tract metaplasia, dysplasia, and carcinoma

“…1,3 In mouse models, dysfunctional telomeres have been shown to induce chromosome instability, leading to chromosomal deletions, amplifications, and rearrangements of the type often found in human biliary carcinomas. 10,11,[22][23][24][25] We therefore examined telomere length in biliary tract carcinomas, as well as in inflammation, metaplasia, and dysplasia of the gallbladder, in order to identify potential molecular changes in telomeres in biliary cancer and biliary cancer precursor lesions. We identified shortened telomeres in metaplastic epithelium (63%) and dysplastic epithelium (90%) of the gallbladder, and infiltrating adenocarcinoma of the gallbladder, intrahepatic bile ducts (cholangiocarcinoma), and extrahepatic bile ducts (98%).…”

Chromosome 1q21 amplification and oncogenes in hepatocellular carcinoma

“…Chromosomal abnormalities may lead to the inactivation of tumor suppressor genes (TSGs) or activation of oncogenes via amplification. As listed in Table 1, chromosomal losses are frequently detected in HCC patients at 1p (36%-37%), 4q (32%-70%), 6q (19%-37%), 8p (26%-77%), 13q (16%-55%), 16p (14%-70%), and 17p (10%-60%) while gains are often detected at 1q (46%-86%), 6p (20%-33%), 8q (31%-83%), 17q (29%-48%), and 20q (5%-37%) [13][14][15][16][17][18][19][20][21][22] . In particular, gain of chromosome 1q21-23 and 8q22-24 has been associated with the early development of HCC [16,23] , whereas gain of 3q has been linked to tumor recurrence and poor overall patient survival [24] .…”