LKB1 as the ghostwriter of crypt history

Marnix Jansen, Danielle Langeveld, Wendy W.J. De Leng, Anya N.A. Milne, Francis M. Giardiello, G. Johan A. Offerhaus

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)437-446
Number of pages10
JournalFamilial Cancer
Volume10
Issue number3
DOIs
StatePublished - Sep 2011

Keywords

  • Clonal evolution
  • Hamartoma
  • LGR5
  • LKB1
  • Peutz-Jeghers syndrome
  • Polyp

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Genetics(clinical)
  • Cancer Research

Fingerprint Dive into the research topics of 'LKB1 as the ghostwriter of crypt history'. Together they form a unique fingerprint.

Cite this