From somatic mutation to early detection: insights from molecular characterization of pancreatic cancer precursor lesions

• Published in: The Journal of pathology 2018-12, Vol.246 (4), p.395-404
• Main Authors: Fischer, Catherine G, Wood, Laura D
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; cancer genomics; Carcinoma in Situ - genetics; Carcinoma in Situ - metabolism; Carcinoma in Situ - pathology; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; driver gene; Early Detection of Cancer - methods; Genetic Heterogeneity; Genetic Predisposition to Disease; Genetic transformation; Humans; intraductal papillary mucinous neoplasm; Lesions; Molecular Diagnostic Techniques; mucinous cystic neoplasm; Mutation - genetics; Neoplasms, Cystic, Mucinous, and Serous - genetics; Neoplasms, Cystic, Mucinous, and Serous - metabolism; Neoplasms, Cystic, Mucinous, and Serous - pathology; Pancreas; Pancreatic cancer; pancreatic cancer precursor lesion; Pancreatic Intraductal Neoplasms - genetics; Pancreatic Intraductal Neoplasms - metabolism; Pancreatic Intraductal Neoplasms - pathology; pancreatic intraepithelial neoplasia; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Phenotype; Precancerous Conditions - genetics; Precancerous Conditions - metabolism; Precancerous Conditions - pathology; Risk Factors; somatic mutation; Tumorigenesis; Tumors
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.5154

Pancreatic cancer arises from noninvasive precursor lesions, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), and mucinous cystic neoplasm (MCN), which are curable if detected early enough. Recently, these types of precursor lesions have been extensively characterized at the molecular level, defining the timing of critical genetic alterations in tumorigenesis pathways. The results of these studies deepen our understanding of tumorigenesis in the pancreas, providing novel insights into tumor initiation and progression. Perhaps more importantly, they also provide a rational foundation for early detection approaches that could allow clinical intervention prior to malignant transformation. In this review, we summarize the results of comprehensive molecular characterization of PanINs, IPMNs, and MCNs and discuss the implications for cancer biology as well as early detection. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.