The Discoveries

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The Genetics of Pancreatic Cancer

--The Discoveries

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Mutations and the
Cell Cycle

Allelotype of Pancreatic
Cancer

Cell Line Mutation
Profiles

TGF-beta and activin
Receptors

BRCA2 Gene

LKB1/STK11 Gene

Telomeric and Mitochondrial DNA

Various Chromosomes

FISH picture

Technical section:
RDA Protocol

Allelotype Markers

The laboratory has defined the frequency and positions of deletions of chromosomal material, and discovered highly frequent mutational changes affecting the DPC4 gene, p16 gene, and p53 gene. K-ras gene mutations are known to be common in pancreatic cancer. Mutant K-ras genes were present in the stool samples of patients with either pancreatic cancer or the precursor lesions for the cancer. A genetic link with familial breast cancer was discovered. Their work has suggested a model for the biology of pancreatic cancer, shown at left in the Mutations and the Cell Cycle link.

So, what does an individual pancreatic cancer look like when we view it with the lenses provided by the molecular genetic technology? Basically, it's a genetic mess. But it's a mess with underlying patterns, which they are now beginning to unravel. You can visualize the patterns through a brief tour of the Allelotype or of the Cell Line Mutation Profiles in the links to the left. Or review the roles of individual genes and chromosomes in pancreatic cancer through their links.

Pancreatic cancer was shown to be distinctively different from another well-studied gastrointestinal cancer type, colon cancer. APC gene mutations, seen in most colon neoplasms, are not found in pancreatic cancer. Also, a DNA mismatch repair defect, seen in 15% of colorectal cancer, is uncommon in pancreatic cancer. This research group therefore does not see pancreatic cancer as being modeled after any other cancer type. It is its own, very characteristic, entity. The aggressiveness of the disease exceeds that of most other carcinomas. Chemotherapeutic agents which may be active against other malignancies do not work effectively when used for pancreatic cancer. The laboratory therefore pursues a focused attempt to study pancreatic cancer as comprehensively and efficiently as can be achieved.