Chromosomal abnormalities of adenocarcinoma of the pancreas: identifying early and late changes.
The high level of karyotypic complexity found in epithelial neoplasms hinders the characterization of their cytogenetic evolution. Derivation of such pathways in adenocarcinoma of the pancreas has been particularly limited, because only a few pancreatic carcinomas are resected at an early stage of disease and so the number of primary carcinomas for which analysis of abnormal karyotypes has been reported is small. Here we report the clonal karyotypic abnormalities identified by G-banding analysis of 36 primary pancreatic carcinomas obtained from patients undergoing a Whipple resection with curative intent. The majority of the 36 carcinomas were diploid or triploid (33 of 36; 91%). Numerical alterations were found in all carcinomas for which a complete karyotype was determined. All the chromosomes were involved in gain, loss, or both gain and loss of the entire chromosome, in at least 8 and up to 28 of the carcinomas. Most commonly lost were chromosomes 18 (in 78% of the 36 carcinomas), 17 (56%), 6 (44%), 21 (42%), 22 (42%), Y (36%), and 4 (33%). Gain of chromosome 20 was observed in 10 of the 36 carcinomas. Structural abnormalities were common, resulting in partial chromosomal gains and losses, with a median number of 7 partial imbalances per carcinoma (range, 1-15). Sixteen carcinomas contained double-minute chromosomes, homogeneously staining regions, or both, indicating gene amplification. Pooling data for these 36 carcinomas with the primary carcinomas with karyotypes published in the Mitelman database (http://cgap.nci.nih.gov/Chromosomes/Mitelman), we defined pathways of karyotypic evolution. The most frequent chromosomal imbalances were -18 (67.6%), -10 (34.3%), -4 (31.4%), +20 (31.4%), -15p (23.8%), -14p (22.9%), +2 (21.9%), -5 (21.9%), -13p (20%), +16 (20%), -21p (19%), -17p (19%), +1q (19.0%). Recurrent imbalances identified as occurring early were -1p, -15p, -18, -7q, -8p, -17p, and -5; late recurrent imbalances were +11q, +7q, +6p, -19p, and +2. In contrast to reports from similar analyses in other epithelial carcinomas, we did not find evidence for multiple karyotypic evolutionary pathways.
Kowalski
Jeanne
J
Department of Oncology, The Johns Hopkins University, Baltimore, MD, USA.
Morsberger
Laura A
LA
Blackford
Amanda
A
Hawkins
Anita
A
Yeo
Charles J
CJ
Hruban
Ralph H
RH
Griffin
Constance A
CA
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D030541:Databases, Genetic; D005821:Genetic Techniques; D006801:Humans; D007621:Karyotyping; D008957:Models, Genetic; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D011003:Ploidies; D013997:Time Factors