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New Developments in the Molecular Mechanisms of Pancreatic Tumorigenesis

Felsenstein, Matthäus, MD; Hruban, Ralph, H., MD; Wood, Laura, D., MD, PhD

Advances In Anatomic Pathology: March 2018 - Volume 25 - Issue 2 - p 131–142
doi: 10.1097/PAP.0000000000000172
Review Articles

Pancreatic cancer is an aggressive disease with a dismal prognosis in dire need of novel diagnostic and therapeutic approaches. The past decade has witnessed an explosion of data on the genetic alterations that occur in pancreatic cancer, as comprehensive next-generation sequencing analyses have been performed on samples from large cohorts of patients. These studies have defined the genomic landscape of this disease and identified novel candidates whose mutations contribute to pancreatic tumorigenesis. They have also clarified the genetic alterations that underlie multistep tumorigenesis in precursor lesions and provided insights into clonal evolution in pancreatic neoplasia. In addition to these important insights into pancreatic cancer biology, these large scale genomic studies have also provided a foundation for the development of novel early detection strategies and targeted therapies. In this review, we discuss the results of these comprehensive sequencing studies of pancreatic neoplasms, with a particular focus on how their results will impact the clinical care of patients with pancreatic cancer.

Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD

Supported by NIH/NCI P50 CA62924; NIH/NIDDK K08 DK107781; Sol Goldman Pancreatic Cancer Research Center; Buffone Family Gastrointestinal Cancer Research Fund; Kaya Tuncer Career Development Award in Gastrointestinal Cancer Prevention; AGA-Bernard Lee Schwartz Foundation Research Scholar Award in Pancreatic Cancer; Sidney Kimmel Foundation for Cancer Research Kimmel Scholar Award; AACR-Incyte Corporation Career Development Award for Pancreatic Cancer Research; Rolfe Pancreatic Cancer Foundation; Joseph C Monastra Foundation; The Gerald O Mann Charitable Foundation (Harriet and Allan Wulfstat, Trustees).

Dr. Wood is a paid consultant for Personal Genome Diagnostics. The remaining authors have no funding or conflicts of interest to disclose.

Reprints: Laura D. Wood, MD, PhD, Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, CRB2 Room 345, 1550 Orleans Street, Baltimore, MD 21231 (e-mail:

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