LADROUE , Charline

BACKGROUND: Congenital secondary erythrocytoses are due to deregulation of hypoxia inducible factor resulting in overproduction of erythropoietin. The most common germline mutation identified in the hypoxia signaling pathway is the Arginine 200-Tryptophan mutant of the von Hippel-Lindau tumor suppressor gene, resulting in Chuvash polycythemia....

The classic model of tumor suppression implies that malignant transformation requires full "two-hit"inactivation of a tumor-suppressor gene. However, more recent work in mice has led to the proposal of a"continuum" model that involves more fluid concepts such as gene dosage-sensitivity and tissue specificity.Mutations in the tumor-suppressor...