JCM Funded Research
GROUND BREAKING RESEARCH – Genetic Study Reveals Large Window of Opportunity for the Early Detection of Pancreatic Cancer
Pancreatic cancer develops and spreads much more slowly than scientists have thought, according to new research from the laboratory of Dr. Christine Iacobuzio-Donahue M.D. Ph.D., Associate Professor of Pathology, Oncology and Surgery at Hopkins’ Sol Goldman Pancreatic Cancer Research Center. Using whole genome sequencing data generated from the cancer tissues of seven patients who underwent a rapid autopsy, Dr. Iacobuzio and colleagues found that it takes at least a decade after the first cancer-causing mutation occurs in a normal cell in the pancreas until the development of a full-fledged cancer cell.
“For the first time, we have a quantifiable estimate of the development of pancreatic cancer, and when it would be best to intervene,” according to Dr. Iacobuzio, “so there is potentially a very broad window for screening.”
The developmental transcription factor Gata4 is overexpressed in pancreatic ductal adenocarcinoma
Matthew S. Karafin1, Christopher T. Cummings1, Baojin Fu1, Christine A. Iacobuzio-Donahue1,2
Departments of 1Pathology and 2Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
Abstract: GATA4 is a transcription factor that plays a role in regulating the normal development of many mesoderm and endoderm derived tissues, including the pancreas. Silencing of GATA4 mRNA expression by promoter methyla- tion has been implicated in carcinogenesis of the ovary, lung and colorectum. By contrast, GATA4 mRNA expression is upregulated in pancreatic cancer cell lines and tissues. To further clarify the relationship of GATA4 to pancreatic cancer, we immunolabeled 90 samples of pancreatic ductal adenocarcinoma using a GATA4 specific monoclonal antibody. Both the intensity and percent of labeling was recorded for each carcinoma and correlated to the clinico- pathologic features available for each patient. Read More
Ongoing Current Research
The NFPTR is a research study aimed at identifying the causes of pancreatic cancer.
Just as we inherit our hair color and our eye color from our parents, so too do some people inherit an increased risk of developing pancreatic cancer. Most of the genes involved are not known, but some are. For example, inherited mutations in the second breast cancer gene (BRCA2) predispose to both breast cancer and pancreatic cancer. To learn more about this important subject visit: http://pathology.jhu.edu/pancreas/nfptr/index.php
The National Familial Pancreas Tumor Registry (NFPTR)
Dr. Ralph Hruban established this research registry at The Johns Hopkins Hospital in 1994. He started the Registry so that scientists and doctors could learn more about pancreatic tumors. Over the past 14 years, the NFPTR has been a leader in the study of familial pancreatic cancer. There have been over 50 peer-reviewed publications that have stemmed from the NFPTR. These data have helped us:
• Demonstrate that individuals with a family history of pancreatic cancer are at an increased risk of developing pancreatic tumors.
• Understand the genetic basis (both inherited and non-inherited) of pancreatic cancer. Demonstrate that genes are an important cause of pancreatic cancer.
• Develop tools to identify individuals at high risk of pancreatic cancer.
• Show that pancreatic tumors can be detected early in high-risk individuals.
The fundamental hypothesis studied in the basic science research laboratories at Johns Hopkins is that cancer of the pancreas is caused by the accumulation of genetic changes (called mutations) in cancer-causing genes and that an improved understanding of these genetic mutations will lead to new techniques to diagnose and treat this cancer. Current research studies include:
1. Basic Science Embryology
Dr. Steven Leach, Department of Surgery
2. Genetics Studies
Dr. Scott Kern, Department of Oncology and Pathology
Dr. Constance Griffin
3. Family Studies
Dr. Alison Klein, Department of Oncology and Pathology
4. Precursor Lesions
Dr. Ralph Hruban, Department of Pathology and Oncology
Dr. Michael Goggins, Early Detection Laboratory
Dr. Akhilesh Pandey
6. New Treatments
Drs. Anirban Maitra and Manual Hidalgo
Drs. Elizabeth Jaffee and Dan Laheru
7. Advanced/Metastatic Disease
Dr. Christine Iacobuzio-Donahue
In 2003, the Gastrointestinal Cancer Rapid Medical Donation Program (GICRMDP) was initiated at The Johns Hopkins Medical Institutions to supplement ongoing research of pancreatic cancer. The principal investigator of this program, Dr. Christine Iacobuzio-Donahue, is committed to studying pancreatic cancers that have spread (“metastasized”) to organs beyond the pancreas. Information gathered from the pancreatic cancer tissues collected at autopsy will form the basis for research directed towards the creation of new drugs to specifically target late stage pancreatic cancers.