caa a22 4500 445330872 CHVBK 20180317142737.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s10689-011-9469-3 doi (NATIONALLICENCE)springer-10.1007/s10689-011-9469-3 LKB1 as the ghostwriter of crypt history [Elektronische Daten] [Marnix Jansen, Danielle Langeveld, Wendy De Leng, Anya Milne, Francis Giardiello, G. Offerhaus] Familial cancer syndromes present rare insights into malignant tumor development. The molecular background of polyp formation and the cancer prone state in Peutz-Jeghers syndrome remain enigmatic to this day. Previously, we proposed that Peutz-Jeghers polyps are not pre-malignant lesions, but an epiphenomenon to the malignant condition. However, Peutz-Jeghers polyp formation and the cancer-prone state must both be accounted for by the same molecular mechanism. Our contribution focuses on the histopathology of the characteristic Peutz-Jeghers polyp and recent research on stem cell dynamics and how these concepts relate to Peutz-Jeghers polyposis. We discuss a protracted clonal evolution scenario in Peutz-Jeghers syndrome due to a germline LKB1 mutation. Peutz-Jeghers polyp formation and malignant transformation are separately mediated through the same molecular mechanism played out on different timescales. Thus, a single mechanism accounts for the development of benign Peutz-Jeghers polyps and for malignant transformation in Peutz-Jeghers syndrome. The Author(s), 2011 LKB1 nationallicence Peutz-Jeghers syndrome nationallicence Hamartoma nationallicence LGR5 nationallicence Clonal evolution nationallicence Polyp nationallicence Jansen Marnix Department of Pathology, Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands aut Langeveld Danielle Department of Pathology, University Medical Center, Utrecht, The Netherlands aut De Leng Wendy Department of Pathology, University Medical Center, Utrecht, The Netherlands aut Milne Anya Department of Pathology, University Medical Center, Utrecht, The Netherlands aut Giardiello Francis Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA aut Offerhaus G. Department of Pathology, Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands aut Familial Cancer Springer Netherlands 10/3(2011-09-01), 437-446 1389-9600 10:3<437 2011 10 10689 https://doi.org/10.1007/s10689-011-9469-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10689-011-9469-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Jansen Marnix Department of Pathology, Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Langeveld Danielle Department of Pathology, University Medical Center, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- De Leng Wendy Department of Pathology, University Medical Center, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Milne Anya Department of Pathology, University Medical Center, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Giardiello Francis Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Offerhaus G. Department of Pathology, Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands aut NATIONALLICENCE 773 0- Familial Cancer Springer Netherlands 10/3(2011-09-01), 437-446 1389-9600 10:3<437 2011 10 10689 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer