Groesser, Leopold and Herschberger, Eva and Ruetten, Arno and Ruivenkamp, Claudia and Lopriore, Enrico and Zutt, Markus and Langmann, Thomas and Singer, Sebastian and Klingseisen, Laura and Schneider-Brachert, Wulf and Toll, Agusti and Real, Francisco X. and Landthaler, Michael and Hafner, Christian (2012) Postzygotic HRAS and KRAS mutations cause nevus sebaceous and Schimmelpenning syndrome. NATURE GENETICS, 44 (7). 783-U211. ISSN 1061-4036,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FEUERSTEIN-MIMS-SYNDROME; EPIDERMAL NEVUS; COSTELLO-SYNDROME; SEBORRHEIC KERATOSES; GERMLINE MUTATIONS; SOMATIC MOSAICISM; MAFFUCCI SYNDROME; FGFR3 MUTATIONS; OLLIER DISEASE; HUMAN SKIN; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie Medicine > Lehrstuhl für Humangenetik Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 May 2020 04:58 |
| Last Modified: | 12 May 2020 04:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18517 |
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