Biochemical characterization of novel germline BRAF and MEK mutations in cardio-facio-cutaneous syndrome.

摘要: Cardio-facio-cutaneous syndrome (CFC) is a sporadic, complex developmental disorder involving characteristic craniofacial features, cardiac defects, ectodermal abnormalities, growth deficiency, hypotonia, and delay. CFC caused by alteration of activity through the mitogen-activated protein kinase (MAPK) pathway due to heterogeneous de novo germline mutations in B-Raf mutant proteins, MEK1 MEK2. Approximately 75% individuals with have BRAF. In vitro functional studies demonstrate that many these confer increase upon as compared wildtype protein. However, seen cancer, some proteins are impaired. Western blot analyses corroborate assays determined phosphorylating downstream effectors MEK ERK. 25% either or MEK2 lead increased judged phosphorylation its effector Unlike BRAF, no somatic ever been identified genes. The identification novel BRAF will help understand pathophysiology this syndrome. Furthermore, it also provide insight normal function MEK, contribute knowledge role MAPK cancer. Since has studied intensively context numerous therapeutics specifically target may merit investigation population patients.