The Sol Goldman Pancreatic Cancer Research Center

The Genetics of Pancreatic Cancer

The Discoveries

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.

NPF Donation The establishment of a new medical research laboratory is always an exciting venture. It is gratifying to know that the participants of the Johns Hopkins Pancreatic Cancer Web chat room helped fund the creation of the lab, and this group -- now known as PanCAN are witnessing the lab's research results into pancreatic cancer. Recently, the lab also received support from the National Pancreas Foundation (see photo).

There are many new challenges. With the limited funding available for pancreatic cancer research, there are few research groups studying pancreatic cancer. Fewer still whose goal is to detect the disease early. Not only do we want to learn more about the disease; we want to help high-risk individuals detect the disease at an early asymptomatic stage, before it is too late.

The Research

The laboratory has been taking several approaches towards the goal of early detection. We have also recruited several committed researchers to the lab.

We are studying gene expression patterns of pancreatic cancers using microarray technology. We are also studying DNA methylation patterns looking for genes that are methylated in pancreatic cancer but not in normal cells.

We have put together a profile of genes that are methylated in pancreatic cancer. Some pancreatic cancers methylate a lot of genes; most appear to methylate only a few genes. We are currently directing our efforts to identify additional genes methylated in pancreatic cancer using novel techniques. We are also studying the role of telomerase in pancreatic cancer and its potential as a marker for early detection.

The People

Dr. Michael GogginsDr. Michael Goggins is the Director of the Pancreatic Cancer Early Detection Laboratory. Dr. Goggins is currently an Associate Professro Professor of Pathology, Medicine, and Oncology. He is a Gastroenterologist and molecular biologist. He obtained his medical degree in 1988 from the Trinity College Dublin. He did his Internal Medicine residency and fellowship in Gastroenterology in St. James' hospital, Dublin. He came to Johns Hopkins in 1995 as a research fellow to join Dr. Scott Kern's pancreas cancer research laboratory at Johns Hopkins and opened the early detection laboratory in February of 1999.