title: LKB1 as the ghostwriter of crypt history.
abstract: 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.
authors.affiliation: Department of Pathology, Academic Medical Center, PO Box 22660, 1100 DD, Amsterdam, The Netherlands. M.Jansen@amc.uva.nl
authors.forename: Marnix
authors.initials: M
authors.lastname: Jansen
authors.forename: Danielle
authors.initials: D
authors.lastname: Langeveld
authors.forename: Wendy W J
authors.initials: WW
authors.lastname: De Leng
authors.forename: Anya N A
authors.initials: AN
authors.lastname: Milne
authors.forename: Francis M
authors.initials: FM
authors.lastname: Giardiello
authors.forename: G Johan A
authors.initials: GJ
authors.lastname: Offerhaus
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D058739:Aberrant Crypt Foci / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D010580:Peutz-Jeghers Syndrome / Q000378:metabolism* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases