Characterizing karyotypic evolution in adenocarcinoma of the pancreas. C. Griffin^1,2, J. Kowalski², L. Morsberger¹, A. Hawkins¹, A. Blackford², C. Yeo³, R. Hruban^1,2. 1) Pathology; 2) Oncology; 3) Surgery, Johns Hopkins University, Baltimore, MD.
   The high level of karyotypic complexity found in epithelial tumors makes it difficult to characterize cytogenetic evolution. Derivation of such pathways in adenocarcinoma of the pancreas also has been limited because virtually no tumors are resected at an early stage of disease. In addition, the number of primary tumors for which analysis of abnormal karyotypes has been reported is small. We report clonal karyotypic abnormalites from G-band analysis of 36 primary pancreas carcinomas. 91% of the tumors were diploid or triploid. Numerical alterations were common. All chromosomes were involved in gain and/or loss in at least 8 and up to 28 tumors. Chr 18, 17, 6, 21, 22, Y & 4 were most commonly lost in 28, 20, 16, 15, 15, 13 & 12 tumors respectively. Gain of chr 20 was found in 10 carcinomas. Structural abnormalities were common, with a median number of 7 imbalances (excluding whole chromosome loss) per tumor (range 1-15). 16 tumors had dms and/or hsrs, indicating gene amplification. Adding these tumors to those published in the Mitleman database (http://cgap.nci.nih.gov/Chromosomes/CytList) we used statistical methods to begin to determine pathways of karyotypic evolution. Based on analyses of 105 tumor samples (44 with 2N ploidy; 61 with not 2N ploidy) from 9 studies, the number of imbalances (sum of the number of losses and/or gains) per chromosome & tumor was calculated & categorized as either none or at least one imbalance. A test of the null hypothesis of no difference in the percent imbalances between 2N ploidy vs. not 2N ploidy tumors, among all chromosomes was rejected (p=0.005), indicating a higher percent of imbalances among not 2N ploidy tumors (60%) vs. 2N ploidy (25%). Chromosomes 10, 16, 22, 8 & 15 were identified as contributing to such a difference. In this analysis, information from ploidy was used as a marker of evolution to address the question of whether there is any particular evolutionary advantage to being diploid. Results from analyses of the temporal evolution of these samples, irrespective of ploidy will be compared.