Postzygotic HRAS and KRAS mutations cause nevus sebaceous and Schimmelpenning syndrome.

Authors: Groesser, L  Herschberger, E  Ruetten, A  Ruivenkamp, C  Lopriore, E  Zutt, M  Langmann, T  Singer, S  Klingseisen, L  Schneider-Brachert, W  Toll, A  Real, FX  Landthaler, M  Hafner, C 
Citation: Groesser L, etal., Nat Genet. 2012 Jun 10;44(7):783-7. doi: 10.1038/ng.2316.
Pubmed: (View Article at PubMed) PMID:22683711
DOI: Full-text: DOI:10.1038/ng.2316

Nevus sebaceous is a common congenital cutaneous malformation. Affected individuals may develop benign and malignant secondary tumors in the nevi during life. Schimmelpenning syndrome is characterized by the association of nevus sebaceous with extracutaneous abnormalities. We report that of 65 sebaceous nevi studied, 62 (95%) had mutations in the HRAS gene and 3 (5%) had mutations in the KRAS gene. The HRAS c.37G>C mutation, which results in a p.Gly13Arg substitution, was present in 91% of lesions. Nonlesional tissues from 18 individuals had a wild-type sequence, confirming genetic mosaicism. The HRAS c.37G>C mutation was also found in 8 of 8 associated secondary tumors. Mosaicism for HRAS c.37G>C and KRAS c.35G>A mutations was found in two individuals with Schimmelpenning syndrome. Functional analysis of HRAS c.37G>C mutant cells showed constitutive activation of the MAPK and PI3K-Akt signaling pathways. Our results indicate that nevus sebaceous and Schimmelpenning syndrome are caused by postzygotic HRAS and KRAS mutations. These mutations may predispose individuals to the development of secondary tumors in nevus sebaceous.

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CRRD ID: 11098548
Created: 2016-06-08
Species: All species
Last Modified: 2016-06-08
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.