15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Diversity of Precursor Lesions For Pancreatic Cancer: The Genetics and Biology of Intraductal Papillary Mucinous Neoplasm

      systematic-review

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Pancreatic ductal adenocarcinoma (PDA), one of the most lethal cancers worldwide, is associated with two main types of morphologically distinct precursors—pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). Although the progression of PanIN into invasive cancer has been well characterized, there remains an urgent need to understand the biology of IPMNs, which are larger radiographically detectable cystic tumors. IPMNs comprise a number of subtypes with heterogeneous histopathologic and clinical features. Although frequently remaining benign, a significant proportion exhibits malignant progression. Unfortunately, there are presently no accurate prognosticators for assessing cancer risk in individuals with IPMN. Moreover, the fundamental mechanisms differentiating PanIN and IPMN remain largely obscure, as do those that distinguish IPMN subtypes. Recent studies, however, have identified distinct genetic profiles between PanIN and IPMN, providing a framework to better understand the diversity of the precursors for PDA. Here, we review the clinical, biological, and genetic properties of IPMN and discuss various models for progression of these tumors to invasive PDA.

          Related collections

          Most cited references97

          • Record: found
          • Abstract: found
          • Article: not found

          Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse.

          To evaluate the role of oncogenic RAS mutations in pancreatic tumorigenesis, we directed endogenous expression of KRAS(G12D) to progenitor cells of the mouse pancreas. We find that physiological levels of Kras(G12D) induce ductal lesions that recapitulate the full spectrum of human pancreatic intraepithelial neoplasias (PanINs), putative precursors to invasive pancreatic cancer. The PanINs are highly proliferative, show evidence of histological progression, and activate signaling pathways normally quiescent in ductal epithelium, suggesting potential therapeutic and chemopreventive targets for the cognate human condition. At low frequency, these lesions also progress spontaneously to invasive and metastatic adenocarcinomas, establishing PanINs as definitive precursors to the invasive disease. Finally, mice with PanINs have an identifiable serum proteomic signature, suggesting a means of detecting the preinvasive state in patients.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Pancreatic cancer biology and genetics.

            Pancreatic ductal adenocarcinoma is an aggressive and devastating disease, which is characterized by invasiveness, rapid progression and profound resistance to treatment. Advances in pathological classification and cancer genetics have improved our descriptive understanding of this disease; however, important aspects of pancreatic cancer biology remain poorly understood. What is the pathogenic role of specific gene mutations? What is the cell of origin? And how does the stroma contribute to tumorigenesis? A better understanding of pancreatic cancer biology should lead the way to more effective treatments.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma.

              Tumors are largely classified by histologic appearance, yet morphologic features do not necessarily predict cellular origin. To determine the origin of pancreatic ductal adenocarcinoma (PDA), we labeled and traced pancreatic cell populations after induction of a PDA-initiating Kras mutation. Our studies reveal that ductal and stem-like centroacinar cells are surprisingly refractory to oncogenic transformation, whereas acinar cells readily form PDA precursor lesions with ductal features. We show that formation of acinar-derived premalignant lesions depends on ectopic induction of the ductal gene Sox9. Moreover, when concomitantly expressed with oncogenic Kras, Sox9 accelerates formation of premalignant lesions. These results provide insight into the cellular origin of PDA and suggest that its precursors arise via induction of a duct-like state in acinar cells. Copyright © 2012 Elsevier Inc. All rights reserved.
                Bookmark

                Author and article information

                Journal
                Clin Transl Gastroenterol
                Clin Transl Gastroenterol
                Clinical and Translational Gastroenterology
                Nature Publishing Group
                2155-384X
                April 2017
                06 April 2017
                1 April 2017
                : 8
                : 4
                : e86
                Affiliations
                [1 ]Massachusetts General Hospital Cancer Center and Harvard Medical School , Boston, Massachusetts, USA
                [2 ]Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital , Sapporo, Hokkaido, Japan
                Author notes
                [* ]Division of Cancer Research, Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital , 3-1, North-33, East-14, Higashi-Ku, Sapporo, Hokkaido 065-0033, Japan. E-mail: ymizu_ccbr@ 123456tohtoku.jp or ymizukami@ 123456mgh.harvard.edu
                Article
                ctg20173
                10.1038/ctg.2017.3
                5415899
                28383565
                9f0ee9ba-b8c6-4f26-b7ab-293bf9778a71
                Copyright © 2017 The Author(s) the American College of Gastroenterology

                Clinical and Translational Gastroenterology is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

                History
                : 23 July 2016
                : 03 January 2017
                Categories
                Clinical and Systematic Reviews

                Gastroenterology & Hepatology
                Gastroenterology & Hepatology

                Comments

                Comment on this article