Genetic alterations in human pancreatic cancer

Pancreatic cancer is a malignant disease with one of the poorest prognoses in the world. A 5-year survival rate of only 6.6% was reported in Japan. In order to establish efficient methods to improve survival rate of this disease, it is indispensable to understand the molecular mechanism of tumorigenesis in the pancreas. We investigated genetic alterations in pancreatic cancer by means of analyzing loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH), and/or comparative genomic hybridization (CGH), and found frequent genetic imbalances in chromosome arms 1p (32%), 6q (37%), 9p (50%), 12q (30%), 17p (59%); 18q (35%), and 20q (93%). We further focused on 6q, 12q, and 20q, and identified small regions of common allelic loss in 6q21 (1-cM): 6q23.3-q24.1 (2-cM), and 12q22-q23.1 (1-cM), and gain of 20q (by 5 to 8 copies per cell). Microsatellite instability (MI) was also analyzed, and high frequency of MI was found in pancreatic cancers. In tumors with MI(+), mutations of the transforming growth factor beta receptor type II (RII) gene were screened. However, no mutations of XII were detected in any of the tumors.