Biliary tract cancers carry dismal prognoses. It is commonly understood that chromosomal aberrations in cancer cells have prognostic and therapeutic implications. However, in biliary tract cancers the genetic changes have not yet been sufficiently studied. The aim of this study was to clarify the presence of mutations in specific chromosomal regions that are likely to harbor previously unknown genes with a significant role in the genesis of biliary tract cancer. The recently developed bacterial artificial chromosome (BAC) array comparative genomic hybridization (CGH) can facilitate detail analysis with high resolution and sensitivity. We applied this to 12 cancer cell lines of the gallbladder (GBC) and the bile duct (BDC) using a genome-wide scanning array. Cell line DNA was labeled with green colored Cy5 and reference DNA derived from normal human leucocytes was labeled with red colored Cy3. GBC, as well as BDC cell lines, have shown DNA copy number abnormalities (gain or loss). In each of the seven GBC cell lines, the DNA copy number was gained on 6p21.32 and was lost on 3p22.3, 3p14.2, 3p14.3, 4q13.1, 22q11.21, 22q11.23, respectively. In five BDC cell lines, there were DNA copy number gains on 7p21.1, 7p21.2, 17q23.2, 20q13.2 and losses were on 1p36.21, 4q25, 6q16.1, 18q21.31, 18q21.33, respectively. The largest region of gain was observed on 13q14.3-q21.32 (≈11 Mb) and of loss on 18q12.2-q21.1 (≈15 Mb), respectively. Both GBC and BDC cell lines have DNA copy number abnormalities of gains and/or losses on every chromosome. We were able to determine the genetic differences between gallbladder and bile duct cancer cell lines. BAC array CGH has a powerful potential application in the screening for DNA copy number abnormalities in cancer cell lines and tumors.

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