The Sol Goldman Pancreatic Cancer Research Center

Advances and Discoveries Made at Johns Hopkins

Precancers in Patients with a Family History
One of the first steps in developing an early detection test for a cancer is understanding the precancerous lesions from which the cancers arise. Dr. C. Shi and colleagues carefully studied the pancreases resected from a series of patients with a strong family history of pancreatic cancer and found that individuals with a strong family history have many more precancerous lesions in their pancreas than do patients without a family history. This study suggests that it may be easier to identify precancerous lesions early in individuals with a strong family history of the disease.

Shi C, Klein AP, Goggins M, Maitra A, Canto M, Ali S, Schulick R, Palmisano E, Hruban RH. Increased prevalence of precursor lesions in familial pancreatic cancer patients. Clin Cancer Res. 15:7737-43, 2009.

Cancer Risk in Families
Approximately 10% of individuals with pancreatic cancer have a family history of the disease. Indeed, news reports suggest that former President Jimmy Carter has a strong family history of pancreatic cancer. Wang and colleagues followed a large series of individuals with a strong family history of pancreatic cancer and found that they are significantly more likely than the general public to develop cancer, including pancreatic cancer, themselves. This study identifies a population (individuals with a family history of pancreatic cancer) who might benefit from early detection screening efforts.

Wang L, Brune KA, Visvanathan K, Laheru D, Herman J, Wolfgang C, Schulick R, Cameron JL, Goggins M, Hruban RH, Klein AP. Elevated cancer mortality in the relatives of pancreatic cancer patients. Cancer Epidemiol Biomarkers Prev. 18:2829-34, 2009.

Protein Markers
Some cancers produce abnormal amounts of specific proteins. These proteins are often then elevated in the blood of patients with that cancer, suggesting that proteins may be effective biomarkers for cancer. Dr. Harsha and colleagues carefully analyzed the literature on pancreatic cancer and they were able to compile a list of proteins that have been reported to be elevated in pancreatic cancer. They published this list as a resource for other investigators working on pancreatic cancer.

Harsha HC, Kandasamy K, Ranganathan P, Rani S, Ramabadran S, Gollapudi S, Balakrishnan L, Dwivedi SB, Telikicherla D, Selvan LD, Goel R, Mathivanan S, Marimuthu A, Kashyap M, Vizza RF, Mayer FJ, DeCaprio JA, Srivastava S, Hanash SM, Hruban RH, Pandey A. A compendium of potential biomarkers of pancreatic cancer. PLOS Medicine Apr 7;6(4):e1000046, 2009.

Predicting Spread
Some pancreatic cancers are locally aggressive, invading local blood vessels, while other pancreatic cancers spread to other organs (they metastastasize). Dr. Iacobuzio-Donahue and colleagues report that mutations in a gene called “SMAD4” may explain this difference. Pancreatic cancers with intact SMAD4 appear to more likely be local problems, while pancreatic cancers with inactivated SMAD4 are more likely to spread to other oragns. Why is this important? It suggests that one day clinicians will be able to test pancreatic cancers for SMAD4 alterations and use the results in their clinical decision making.

Iacobuzio-Donahue CA, Fu B, Yachida S, Luo M, Abe H, Henderson CM, Vilardell F, Wang Z, Keller JW, Banerjee P, Herman JM, Cameron JL, Yeo CJ, Halushka MK, Eshleman JR, Raben M, Klein AP, Hruban RH, Hidalgo M, Laheru D. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol. 27:1806-13, 2009.

PALB2 and Familial Pancreatic Cancer
Approximately 10% of individuals with pancreatic cancer have a family history of the disease. Jones and colleagues discovered one of the genes which, when inherited, can cause pancreatic cancer to run in families. Using genetic sequencing, Jones and colleagues showed that inherited mutations (DNA changes) in the PALB2 gene increase the risk of pancreatic cancer. This suggests that some individuals, especially those with a family history of breast and/or pancreatic cancer may one day benefit from genetic testing.

Jones S, Hruban RH, Kamiyama M, Borges M, Zhang X, Parsons DW, Lin JC, Palmisano E, Brune K, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Parmigiani G, Kern SE, Velculescu VE, Kinzler KW, Vogelstein B, Eshleman JR, Goggins M, Klein AP. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science. 324:217, 2009.

Statement of conflict of interest:
Dr. Hruban and several other authors on this study receive royalty payments from Myriad Genetics for the PALB2 invention