LKB1 as the ghostwriter of crypt history

作者：Jansen Marnix^*; Langeveld Danielle; De Leng Wendy W J; Milne Anya N A; Giardiello Francis M; Offerhaus G Johan A

来源：Familial Cancer, 2011, 10(3): 437-446.

DOI：10.1007/s10689-011-9469-3

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

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.

• 出版日期2011-9