Department of Pathology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
Abnormalities of several oncogenes and tumor suppressor genes
have been identified in carcinomas of the pancreas during the
last decade, and multiple genetic changes have been demonstrated
in individual carcinomas. The variety of genetic changes suggests
that multiple etiologic factors contribute to carcinogenesis
in the pancreas. Several of these changes are characteristically
found in specific types of tumors, suggesting that different
causes and molecular mechanisms are involved. One example is
the loss of heterozygosity at the von Hippel-Lindau (VHL) gene
locus in both wild type and hereditary serous cystadenomas,
and another is the virtual absence of K-
ras mutation and
p53 abnormalities in acinar cell carcinomas, whereas both are frequently
found in ductal adenocarcinomas. Multiple lines of evidence
place
K-ras mutation very early and loss of
p53 and
p16 as late
events during ductal cell carcinogenesis. The timing and order
of other genetic changes such as loss of the
DPC4 tumor suppressor
function is less certain.
