The Sol Goldman Pancreatic Cancer Research Center

The Genetics of Pancreatic Cancer

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 below in the Mutations and the Cell Cycle.

Mutations and the Cell Cycle
Mutations and Cell Cycle
In this figure, the genetic changes of pancreatic cancer are shown in a theoretical framework, emphasizing the disruption of cell cycle controls. Ras mutations provide an inappropriate stimulus for cells to grow in a phase called G1. The p16 and p53 genes act at multiple checkpoint positions to restrict inappropriate G1 progression. DPC4 mutations probably affect this phase as well.

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 shown below. Or review the roles of individual genes and chromosomes in pancreatic cancer.

Allelotype of Pancreatic Cancer
Mutations and Cell Cycle
In this figure, the genetic changes of pancreatic cancer are shown in a theoretical framework, emphasizing the disruption of cell cycle controls. Ras mutations provide an inappropriate stimulus for cells to grow in a phase called G1. The p16 and p53 genes act at multiple checkpoint positions to restrict inappropriate G1 progression. DPC4 mutations probably affect this phase as well.

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.