Growth Factor receptor 3 Mutations in Epidermal Nevi and 成纤维细胞生长因子受体3基因突变与表皮痣ppt课件.ppt

Fibroblast Growth Factor receptor 3 Mutations in Epidermal Nevi and Associated Low Grade l Bladder Tumors.?Hernandez S, Toll A et al?JID (2007, July), Volume 127 ;INTRODUCTION ;Epidermal nevus;Seborrheic keratosis;Acanthosis Nigricans; FGFR3 DNA mutations are found in Skeletal dysplasias (exons 7, 10, 15), and the resultant constitutive kinase activity correlates with disease severity. The authors found a case of a 41 year old patient with a congenital widespread non epidermolytic keratinocytic Epidermal Nevi(in addition to 3 other literature reports). Patient had a history of low grade urothelial carcinoma at age 19. Based on three previous reports of associated UC and EN and the histological resemblances with SK, the authors hypothesize that EN might be caused by FGFR3 mutations. ;MATERIALS AND METHODS ;;RESULTS ;DISCUSSION ;While FGFR3 may contribute to the development of EN and UC, other genes may contribute: -PIK3CA which is associated with low grade UC -PTCH and TSC1 which are altered in skin and bladder tumors.;COMMENTARY (Hafner et al.) (1572-1573) ;Transgenis mice FGFR3 (S249C) mutant develop verrucous skin lesions similar to SK(Logie et al, 2005). The authors went on to identify activating FGFR3 mutations in 39% of Sk lesions. ? Mechanisms causing FGFR3 mutation are unknown but the R248C mutation appears to be a hotspot in EN as it was found by the two studies published in the current issue. The R248C mutation is a C to T transition in the DNA and might be caused by sunlight. Sunlight has been shown to be an independent risk factor for the development of SK(not in EN). ; ;Conclusion of the commentary