The Sol Goldman Pancreatic Cancer Research Center

What's New 2004

Our Sincere Congratulations to Dr. Kern!
December 2004

Our congratulations go out to Dr. Scott Kern. Dr. Kern, a Professor of Oncology and Pathology here at Johns Hopkins, was awarded the first Louis A. Cochet Award for Outstanding Pancreatic Cancer Research. Dr. Kern received this award at a meeting on pancreatic cancer held in Philadelphia on December 1, 2004. This award recognizes Dr. Kern's contribution to the field, including the discovery of the pancreatic cancer gene (DPC4), an advance that led to the discovery of the second breast cancer gene (BRCA2), and for his life's work which has demonstrated that pancreatic cancer is fundamentally a genetic disease (a disease caused by damage to the DNA).



Beta Sigma Donation
November 2004

The Johns Hopkins Pancreas Cancer Research laboratory of Dr. Christine Iacobuzio-Donahue was awarded a grant of $25,000 at the 2004 National Convention of Sigma Beta Sorority, Inc. which met on October 23, 2004. Sigma Beta is a national philanthropic organization that has donated to various deserving organizations since its founding in 1923. This grant will support Dr. Iacobuzio-Donahue's research that strives to better understand the unique molecular features of pancreatic cancer. Information gathered from her research will form a basis for the development of improved methods to treat this lethal disease.



A Fond Farewell
September 7, 2004

With a fond farewell, we wish Kieran Brune, the National Familial Pancreas Tumor Registry (NFPTR) Coordinator from June 2000 to September 2004, the best of luck as she begins medical school at the University College of Dublin, Dublin, Ireland. While at Johns Hopkins in her position as NFPTR coordinator, Kieran has seen the registry grow exponentially during her tenure. Over 1400 families are now enrolled in our studies of familial pancreatic cancer. Kieran took the initiative on a number of projects, including the publication of the first newsletter (NFPTR News) as well as a leadership role in Johns Hopkins collaborations with the national multi-center consortium (PACGENE). She also attended national meetings to represent Dr. Hruban and the NFPTR.

Kieran's compassionate and caring attitude is contagious and touched many of the family's lives in the registry. We wish her continued success in her new endeavors at medical school.

Please join us in welcoming Kieran's replacement, Miriam Tillery. Miriam has spent the past four years working in colon cancer research as a study coordinator. Joining the National Familial Pancreas Tumor Registry as the new coordinator is an exciting opportunity for Miriam to work with patients and their families in their battle against this terrible disease.

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Progress on BRCA2/Fanconi gene mutations in pancreatic cancer
August 2004

Nine years ago, the Kern Laboratory found mutations of a new gene. Soon, this laboratory and others working in other tumor systems found that mutations of the gene were often inherited, raising the risk for pancreatic, ovarian, and breast cancer when an individual inherits one bad copy of the gene. This was the second gene found to cause inherited breast cancer, thus leading to the gene name, BRCA2.

Last year, postdoctoral fellow Michiel van der Heijden of the Kern Laboratory, followed up on that earlier discovery. They knew that BRCA2 was one of the genes that gives rise to a rare syndrome, Fanconi anemia, when two bad copies are inherited by an individual. Fanconi anemia causes skeletal abnormalities and progressive bone marrow failure, and genes other than BRCA2 are responsible for most cases of the syndrome. In each case, one needed to inherit two bad copies in order to develop the syndrome. But what if an individual only inherited one bad copy, a condition that was previously thought to be lacking any association with disease? Was it possible that some of these other Fanconi genes might play a role in pancreatic cancer? Dr. van der Heijden found the answer to be "Yes!" Two of the Fanconi genes, FANCC and FANCG had mutations in a number of pancreatic cancers. Some of these mutations are inherited, meaning that individuals were inheriting a risk for pancreatic cancer. Fanconi anemia gene mutations are found in about 1 in 300 persons in the general population, and in 1 in about 75 Ashkenazi Jews. It remains to be determined how much the risk of cancer increases for such persons, and whether cancers other than pancreatic cancer would be included in the higher risk. Dr. van der Heijden and colleagues had another interesting finding; three of the nine persons whose pancreas cancer had young onset (less than 50 years of age) had such mutations. He perhaps had discovered a fairly common cause of young-onset pancreatic cancer.

At the time, there were no easy tests for the kinds of Fanconi gene mutations now being studied, but such tests may become available in the future. Such testing is likely to be of clinical importance. Cells that are defective in the Fanconi genes are known from other research to be highly sensitive to certain chemicals. In this month's issue of The American Journal of Pathology, Dr. van der Heijden and colleagues report that the Fanconi-deficient pancreatic cancer cells are especially susceptible to the toxic effects of the anticancer drugs mitomycin and cis-platin. If may be possible in the future to recommend individualized therapeutic regimens for patients with these mutations. More research in this exciting new area is underway.

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Johns Hopkins Is Number One Again!!!
July 2004

#1 again!

THE JOHNS HOPKINS HOSPITAL TOPS U.S.NEWS & WORLD REPORT'S "HONOR ROLL" FOR THE 14th YEAR IN A ROW

For the 14th consecutive year, The Johns Hopkins Hospital has topped U.S. News & World Report's rankings of American hospitals.

This year's annual guide reports results of a survey of a hospital's reputation in 17 medical specialties among a national sample of doctors, along with analysis of objective indicators such as death rates, technology, nurse staffing, service mix and discharge planning.

Hopkins again ranked in the top 10 in 16 of the 17 specialty categories listed. In addition to landing at the top of the honor roll, the Hospital ranked #1 in Gynecology, Otolaryngology and Urology; #2 in Geriatrics, Kidney Disease, Neurology/Neurosurgery, Ophthalmology and Rheumatology; #3 in Cancer, Digestive Disorders, Hormonal Disorders, Pediatrics, Psychiatry and Respiratory Disorders; #4 in Heart/Heart Surgery and Orthopedics; and #13 in Rehabilitation For a complete list of all rankings, go to www.usnews.com/usnews/health/hosptl/honorroll.htm.

In a letter announcing the rankings to all employees, Johns Hopkins Medicine Dean/CEO Edward D. Miller, M.D., and Ronald R. Peterson, president of The Johns Hopkins Hospital and Health System, said the recognition is "especially welcome as we labor to build, renew, enrich and expand our services, facilities and safety initiatives." And they again emphasized to all faculty and staff that "neither your contributions nor the magazine's recognition of your commitment is taken for granted."

"While we say it so often, it is still true that this is really a tribute to our Hospital, its wonderful nurses and staff, the School of Medicine's faculty physicians and the many community physicians with whom we have close ties," they added. "It is a worthy acknowledgment of the innovative and compassionate patient care that is Hopkins's hallmark -- and of the people who make that kind of care possible."

Miller and Peterson also commented that "such independent evaluations as these rankings are of growing value to patients, the public, referring physicians and insurers."

Finally, they noted once again that "our presence on the list puts us in great company, and we congratulate all of the medical centers on the magazine's honor roll."

Coming in at #2 on the honor roll was the Mayo Clinic. Rounding out the Honor Roll list, in rank order, are Massachusetts General Hospital; Cleveland Clinic; UCLA Medical Center; Duke University Medical Center and University of California San Francisco (tie); Barnes-Jewish Hospital, St. Louis; New York-Presbyterian Hospital and University of Washington Medical Center, Seattle (tie); University of Michigan Medical Center, Ann Arbor; Brigham and Women's Hospital, Boston; Hospital of the University of Pennsylvania, Philadelphia; and Stanford Hospital and Clinics.

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Screening for Pancreatic Neoplasia in High-risk Individuals: An EUS-based Approach
July 2004

In the July issue of Clinical Gastroenterology Hepatology, Marcia Canto and colleagues from Johns Hopkins report the results of screening for pancreatic cancer in asymptomatic (patients without symptoms) individuals known to be at increased risk because of their family history. Endoscopic ultrasound (EUS) was used. In this technique a small tube with an ultrasound device at the end is inserted through the patient's nose and into the patient's stomach and duodenum. The ultrasound device can then be used to image the pancreas. Thirty-eight patients were screened in Dr. Canto's study and six pancreatic masses were found. Several of these patients went to surgery and one was found to have an early cancer and another a precancerous tumor (intraductal papillary mucinous neoplasm). Therefore, 5.3% or 1 in 20 patients was found to have a clinically important pancreatic mass. This study therefore represents the first step towards demonstrating that screening for early pancreatic cancer is possible.

Clin Gastroenterol Hepatol. 2004 Jul; 2(7):606-21

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National Familial Pancreatic Tumor Registry Update
April 6, 2004

Dr. Klein and colleagues (Cancer Research 64:2634-2638), followed 838 families who participated in the National Familial Pancreatic Tumor Registry to determine how likely were new pancreatic cancer to develop in these families. 22 new pancreatic cancer cases developed in these families, after the family had entered the registry. Dr. Klein found that individuals with three or more first-degree relatives with pancreatic cancer (brothers, sisters, parents or children) were at a 32-fold increase risk of developing pancreatic cancer. Individuals with two first-degree relatives with pancreatic cancer had a 6.5-fold increased risk. This increase in risk was even higher among family members who smoked cigarettes. The results of this study further establish that pancreatic cancer does cluster in families. Additionally, these results help to identify individuals who may benefit from screening for the early signs of pancreatic cancer once reliable screening tests are developed.

To learn more about how you can join the National Familial Pancreas Tumor Registry contact the registry coordinator Kieran Brune (410-955-3502 or e-mail kbrune1@jhmi.edu), or click here.

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Recent publications from Dr. Iacobuzio-Donahue
April 1, 2004

Dr. Iacobuzio-Donahue recently published two exciting articles in Cancer Research. The first article, published in the December 15 issue (Cancer Research 2003; 63:8614-22) describes the largest, most comprehensive study to date of gene expression (the genes made) in pancreatic cancer. Close to 100 samples were analyzed using the most current gene chip (Affemetrix U133). Dr. Iacobuzio-Donahue and colleagues discovered 142 potential new markers of pancreatic cancer. Already, Dr. Koopmann has shown that one of these markers, called "osteopontin," is elevated in the blood of patients with pancreatic cancer (Cancer Epi Biomarkers Prev, 2004; 13:487-91) and Dr. Nichols has demonstrated that another of these markers, claudin 4, may be a useful therapeutic target (Am J Clin Pathol. 2004; 121:226-30).

In the second paper published by Dr. Iacobuzio-Donahue (Cancer Research 2004; 64:871-875) she describes the largest genetic analysis conducted to date of the DNA changes in pancreatic cancer. Dr. Iacobuzio-Donahue and colleagues conducted a large-scale "allelotypes" (an analysis of DNA losses in a cancer) on a series of pancreatic cancers and they discovered a number of hot spots of DNA alterations in pancreatic cancer. These hot spots will help other scientists identify the genes that are targeted for inactivation in pancreatic cancer. An understanding of these genes, in turn, may lead to a better understanding of why pancreatic cancer develops and how to treat it.

References
Iacobuzio-Donahue CA, van der Heijden MS, Baumgartner MR, Troup WJ, Romm JM, Doheny K, Pugh E, Yeo CJ, Goggins MG, Hruban RH, Kern SE. Large-scale allelotype of pancreaticobiliary carcinoma provides quantitiative estimates of genome-wide allelic loss. Cancer Res. 64: 871-875, 2004.

Koopmann J, Fedarko NS, Jain A, Maitra A, Iacobuzio-Donahue C, Rahman A, Hruban RH, Yeo CJ, Goggins M. Evaluation of osteopontin as biomarker for pancreatic adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 13:487-91, 2004.

Iacobuzio-Donahue CA, Cong J, Parmiagiani G, Yeo CJ, Hruban RH, Kern SE. Missense mutations of MADH4: Characterization of the mutational hot spot and functional consequences in human tumors. Clin Cancer Res. 10:1597-1604; 2004.

Nichols LS, Ashfaq R, Iacobuzio-Donahue CA. Claudin 4 protein expression in primary and metastatic pancreatic cancer: support for use as a therapeutic target.Am J Clin Pathol. 121(2):226-30, 2004.

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