The Sol Goldman Pancreatic Cancer Research Center

Advances and Discoveries Made at Johns Hopkins

Classification of Precancers
An international team of pathologists met at the Sol Goldman Pancreatic Cancer Research Center to examine the classification system for precancerous lesions in the pancreas. The group included participants from Japan, Europe and North America. After reviewing the "state of the art," the group proposed a simplified classification scheme that changes the previous three-tier grading system for precursors to a two-tier system. It is hoped that this simplified system will be easier for clinicians to apply in their day to day practice, and it will therefore improve patient care.

Basturk O, Hong SM, Wood LD, Adsay NV, albores-Saavedra J, Biankin AV, Brosens LA, Fukushima N, Goggins M, Hruban RH, Kato Y, Klimstra DS, Klöppel G, Krasinskas A, Longnecker DS, Matthaei H, Offerhaus GH, Shimizu M, Takaori K, Terris B, Yachida S, Esposito I, Furukawa T. A revised classification system and recommendations from the Baltimore consensus meeting for neoplastic precursor lesions in the pancreas. Am J Surg Pathol. 39:1730-41, 2015.

Pancreatic Cancer that has Spread to the Lungs
T. Wangiam and colleagues reported in the journal Oncotarget that some patients with pancreatic cancer who develop metastases that are limited to the lung may be able to achieve longer survival. In the past doctors assumed that any spread (metastasis) of pancreatic cancer portended the patient’s death. Here, Wangiam and colleagues show that not all metastases are the same. Some patients with lung metastases can do well.

Wangjam T, Zhang Z, Zhou XC, Lyer L, Faisal F, Soares KC, Fishman E, Hruban RH, Herman JP, Laheru D, Weiss M, Li M, De Jesus-Acosta A, Wolfgang CL, Zheng L. Resected pancreatic ductal adenocarcinomas with recurrence limited in lung have a significantly better prognosis than those with other recurrence patterns. Oncotarget. 6:36903-10, 2015.

Jumping Genes in Pancreatic Cancer
In two remarkable studies, Drs. N. Rodic and S. Solyom from the Sol Goldman Pancreatic Cancer Research Center reported that transposons (also known as "jumping genes") may play a role in the development of pancreatic cancer. Transposons were discovered years ago by scientists studying maize corn. Here Drs. Rodic and Solyom show how this same cellular process can lead to cancer when it goes a rye. What does this mean to patients with pancreatic cancer? Right now this is purely a "basic science" discovery that adds to the growing body of information on what can cause pancreatic cancer to develop in one person and not another. It has hoped that, in turn, a better understanding of the causes of pancreatic cancer will lead to new was to diagnose and treat this disease.

Rodic N, Steranka JP, Makohon-Moore A, Moyer A, Shen P, Sharma R, Kohutek ZA, Huang CR, Ahn D, Mita P, Taylor MS, Barker NJ, Hruban RH, Iacobuzio-Donahue CA, Boeke JD, Burns KH. Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma. Nat Med. 21:1060-4, 2015.

Ewing AD, Gacita A, Wood LD, Ma F, Xing D, Kim MS, Manda SS, Abril G, Pereira G, Makohon-Moore A, Looijenga LH, Gillis AJ, Hruban RH, Anders RA, Romans KE, Pandey A, Iacobuzio-Donahue CA, Vogelstein B, Kinzler KW, Kazazian HH, Solyom S. Widespread somatic L1 retrotranspostion occurs early during gastrointestinal cancer evolution. Genome Res. 25:1536-45, 2015.

DNA Analysis of Cyst Fluid Can be used to Classify Pancreatic Cysts
Dr. Anne Marie Lennon reported a major advance in the diagnosis of pancreatic cysts in the journal Gastroenterology. Some pancreatic cysts are potential precancerous lesions and they represent an opportunity for early detection and early treatment. Other types of pancreatic cysts are completely harmless, and they represent a potential risk of over treatment (if all of them were removed because doctors thought they were the precancerous type). In an international collaborative effort, Dr. Lennon and colleagues sequenced the DNA in fluid removed from cysts and showed that the DNA changes in the cyst fluid could be used to predict the type of cyst. For example, GNAS and KRAS gene mutations suggest that the cyst is a mucin-producing cyst (an IPMN or MCN) which can be a precursor cyst, while VHL gene mutations suggest that the cyst is a serous cystic neoplasm (a usually harmless type of cyst). Dr. Lennon and colleagues are now working to validate their findings in a larger series of cases. They hope to make this a clinically available test.

Springer S, Wang Y, Mokin MD, Masica DL, Jiao Y, Kinde I, Blackford A, Raman SP, Wolfgang CL…Goggins Ms, Canto MI, Ahuja N, Hirose K, Makary M, Weiss MJ, Cameron J, Pittman M, Eshleman JR, Diaz LA, Papadopoulos N, Kinzler KW, Karchin R, Hruban RH, Vogelstein B, Lennon AM. A combination of molecular markers and clinical fetaures improve the classification of pancreatic cysts. Gastroenterology. 149:1501-10, 2015.

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Long-term Survivors
Dr. Marco dal Molin reported in Clinical Cancer Research an in-depth study of the cancers from patients with pancreatic cancer who survived long-term (greater than five or ten years). Dr. dal Molin and colleagues sequenced all known human genes (the "exomes") in a series of pancreatic cancers and compared the results of this sequencing with the sequencing results of pancreatic cancers resected from patients who survived only short-term after their surgery. Remarkably, the scientists were not able to identify significant differences in cancers from the two groups of patients. What does this mean? It means that there isn’t a simple "one gene" explanation for why some patients survive long-term. The reasons are likely to be complex, and may include factors such as the strength of the immune system.

dal Molin M, Zhang M, de Wilde RF, Ottenhof NA, Rezaee N, Wolfgang CL, Blackford AL, Vogelstein B, Kinzler KW, Papadopoulos N, Hruban RH, Maitra A, Wood LD. Very long-term survival following resection for pancreatic cancer is not explained by commonly mutated genes: results of whole-exome sequencing analysis. Clin Cancer Res. 21:1944-50, 2015.