[Frontiers in Bioscience 3, d1148-1160, November 15, 1998] |
MOLECULAR PATHOBIOLOGY OF PANCREATIC ADENOCARCINOMA
Shamlal Mangray and Thomas C King
Department of Pathology and Laboratory Medicine, Brown University School of Medicine, Providence, RI
Received 8/24/98 Accepted 9/4/98
4. CHROMOSOMAL ABNORMALITIES IN PANCREATIC ADENOCARCINOMA
Cytogenetic analysis of pancreatic tumors has been useful in identifying specific chromosomal abnormalities although most tumors show complex karyotypes with numerous anomalies. G-banded metaphase spreads have suggested that additions to chromosomes 7 and 20, and loss of chromosome arms 1p and 6q are important in the pathogenesis of pancreatic adenocarcinoma (10). Molecular probes specific for each chromosomal arm have been used to refine genetic mapping and allelic loss studies have been helpful in identifying tumor suppressor gene candidates in pancreatic adenocarcinomas. Comprehensive evaluation of 17 pancreatic adenocarcinomas showed a high frequency of non random allelic loss for chromosome arms 1p (50%), 6p (50%), 6q (50%), 8p (56%), 9p (76%), 10p (50%), 10q (50%), 12p (50%), 12q (67%), 17p (95%), 18q (88%), 21q (61%), and 22q (61%) (10). These allelic loss data correlate with known locations of several tumor suppressor genes. Chromosome 17p is the normal location of the p53 tumor suppressor gene, chromosome 18q is the site of the DPC4 gene (and the DCC gene implicated in colorectal carcinoma) and chromosome 9p is the site of the p16INK4a(MTS1) gene. These individual genes and their potential mechanisms of action in the genesis of pancreatic adenocarcinoma are discussed further below.
DNA Ploidy has been investigated by some workers in an effort to select candidates for surgical resection (19). Aneuploid tumors have been reported to be associated with a poorer prognosis than diploid tumors. These data must be interpreted with caution, however, since almost all ductal pancreatic tumors are known to contain multiple genetic abnormalities and are expected to be aneuploid. Ploidy analysis may identify less common, lower grade tumors (e.g. cystadenomas and low grade cystadenocarcinomas) which would be expected to have a significantly better prognosis.