Dr. Christine Iacobuzio-Donahue leads team to major breakthrough – 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. Read More
In vivo and in vitro propagation of intraductal papillary mucinous neoplasms – Scientists at Johns Hopkins are studying a new cell line which they hope will provide them with the ability to develop new approaches to the early detection and treatment of curable tumors in the pancreas. Read More
The Johns Hopkins pancreatic cancer research team will receive two prestigious awards at the 2010 meeting of the American Association of Cancer Research (AACR) held April 17-21, in Washington, D.C.
Dr. Ralph Hruban – 2010 INNOVATOR Award recipient
Zeshaan A. Rasheed, M.D., Ph.D. – PanCan & American Assoc. for Cancer Research Award Grant
New National Pancreatic Cancer Research Consortium – The Lustgarten Foundation has formed a national pancreatic cancer research consortium, a collaborative effort to advance the most promising research initiatives aimed at finding a cure for pancreatic cancer. Scientists participating in the Pancreatic Cancer Research Consortium (PCRC) will share knowledge, information, expertise and technologies in a coordinated effort.
We are pleased that two of the four initial grants were awarded to scientists at Johns Hopkins.
• Early detection – A project led by Bert Vogelstein at the Johns Hopkins University School of Medicine will develop a blood and fluid-based test to detect pancreatic cancer at an early stage, when it may be curable.
• Defining familial pancreatic cancer – An international project led by Ralph Hruban from Johns Hopkins University will study the inherited causes of pancreatic cancer.
Congratulations to the Johns Hopkins Pancreatic Cancer Research team!
To learn more about research into the familial aggregation of pancreatic cancer at Johns Hopkins, visit the NFPTR Web site.
Differential Expression of Multiple Genes in Association with MADH4/DPC4/SMAD4 Inactivation in Pancreatic Cancer.
Dengfeng Cao1, Raheela Ashfaq3, Michael G. Goggins1, Ralph H. Hruban 1, 2, Scott E. Kern2 and Christine A. Iacobuzio-Donahue1, 2
The importance of the transforming growth factor beta (TGF-β)/Activin/Smad signaling pathway is underscored by its suppression of tumorigenesis through activation of downstream genes. Cell functions reportedly regulated by the TGF-β/Activin pathway include cell proliferation, differentiation and death following binding by specific ligands to TGF-β/Activin receptors. Upon binding of ligand (TGF-β, nodal, activin, or bone morphogenic protein BMP), type I and type II TGF-β receptors form heteromeric complexes in which the type II receptor phosphorylates the type I receptor.
Evaluation of GATA-4 and GATA-5 Methylation Profiles in Human Pancreatic Cancers Indicate Promoter Methylation Patterns Distinct from other Human Tumor Types
Pancreatic cancer claims the life of about 33,000 people yearly in the U.S., making it the fourth most common cause of cancer mortality.1 Thus, a better understanding of the multistage carcinogenesis of pancreatic cancer is needed to aid development of early detection strategies and more effective treatments. Regulation of gene expression through promoter CpG island methylation is increasingly appreciated as an important mechanism in controlling embryonic development, aging as well as contributing to carcinogenesis.2 As in other human cancers, pancreatic cancer evolves in part due to profound epigenetic alterations. Silencing of cancer-related genes, especially tumor suppressor genes, by DNA methylation have been widely reported in various cancers, including pancreatic cancer. Read More
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
There are currently few therapeutic options for patients with pancreatic cancer and new insights into the pathogenesis of this lethal disease are urgently needed. Towards this end, we performed a comprehensive genetic analysis of 24 pancreatic cancers. We first determined the sequences of 23,219 transcripts, representing 20,661 protein-coding genes, in these samples. Then, we searched for homozygous deletions and amplifications in the tumor DNA by using microarrays containing probes for ~106 single nucleotide polymorphisms (SNPs). We found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations. These alterations defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67% to 100% of the tumors. Analysis of these tumors’ transcriptomes with next-generation sequencing-by-synthesis technologies provided independent evidence for the significance of these pathways and processes. Read More
DPC4 Gene Status of the Primary Carcinoma Correlates With Patterns of Failure in Patients With Pancreatic Cancer
Contrary to the extensive data accumulated regarding pancreatic carcinogenesis, the clinical and molecular features characteristic of advanced stage (stage III and IV) disease are unknown. A comprehensive study of pancreatic cancers from patients who have succumbed to their disease has the potential to greatly expand our understanding of the most lethal stage of this disease and identify novel areas for intervention. Read More
Immortalizing the Complexity of Cancer Metastasis
Genetic Features of Lethal Metastatic Pancreatic Cancer Obtained from Rapid Autopsy
The virtual lack of well-characterized metastatic pancreatic cancer tissues for study has limited systematic studies of the metastatic process of this deadly disease. To address this important issue, we have instituted a rapid autopsy protocol for the collection of high quality tissues from patients with metastatic pancreatic cancer, called the Gastrointestinal Cancer Rapid Medical Donation Program (GICRMDP). At the time of preparation of this manuscript, 20 patients with metastatic pancreatic cancer and one patient with metastatic colon cancer have undergone a rapid autopsy in association with the GICRMDP. Read More