Germ line-inactivating mutation of Lkb1 leads to Peutz-Jeghers syndrome, which is characterized by benign hamartomas and a susceptibility to malignant epithelial tumors.
Peutz-Jeghers syndrome (PJS) is a dominantly inherited disorder characterized by gastrointestinal hamartomatous polyps and mucocutaneous melanin pigmentation.Germ line mutations in LKB1 cause PJS.
In all cases, the polyps arising in the Lkb1+/- mice were found to be hamartomas that were histologically indistinguishable from polyps resected from PJS patients, indicating that Lkb1+/- mice model human PJS polyposis.
Together, our data rationalize several features of PJS polyposis--notably its peculiar histopathological presentation and limited malignant potential--and place Lkb1 in a distinct class of tumour suppressors.