| Research Abstract |
We first searched for imbalances of copy number in human pancreatic cancer cells using more than 100 primary tumor and corresponding normal tissues as well as 12 cell lines by (i) LOH study with microsatellite markers of all chromosome arms except for short arms of acrocentric chromosomes and sex chromosomes and (ii) comparative genomic hybridization (CGH). Frequent gains of chromosome arms 8q and 20q, and losses of 1p, 6q, 9p, 12q, 17p, and 18q were observed.
We further focused on allelic loss of chromosome arm 12q and constructed a detailed deletion map. Finally we identified a 1-cM region of common allelic loss. We further constructed a contig in this region with YAC and BAC clones, and found that a YAC colne of 790 kb in size harbored the whole region of common allelic loss. We are now constructing a cosmid contig in this region.
Region of the gain of chromosome 8q overlapped with the region of the c-myc oncogene. Region of the gain of chromosome 20q was evaluated for its precise region and copy number by fluorescence in situ hybridization (FISH). Copy number was increased by two-fold, and the region was overlapped with that of breast cancer.
Involvement of DNA mismatch repair error was also analyzed in this study. Frequent microsatellite instability (MI) was observed (13% of the tumors). None of the mutations in hMSH2 and hMLH1 were observed in tumors with MI+.Moreover, somatic mutations of neither the transforming growht factor (TGF) beta receptor type II (RII) gene nor the insulin-like growht factor II receptor (IGFIIR) gene were found which were frequently observed in colorectal, gastric, and endometrial cancers with MI+. These results suggested that mutations of these genes do not play an important role, if any, in pancreatic carcinogenesis.
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