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 language | English (US) |
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Pages (from-to) | 437-446 |
Number of pages | 10 |
Journal | Familial Cancer |
Volume | 10 |
Issue number | 3 |
DOIs | |
State | Published - Sep 2011 |
Externally published | Yes |
Keywords
- Clonal evolution
- Hamartoma
- LGR5
- LKB1
- Peutz-Jeghers syndrome
- Polyp
ASJC Scopus subject areas
- Genetics
- Oncology
- Genetics(clinical)
- Cancer Research