Keratinocytic epidermal nevi are associated with mosaic RAS mutations
Por:
Hafner, C, Toll, A, Gantner, S, Mauerer, A, Lurkin, I, Acquadro, F, Fernandez-Casado, A, Zwarthoff, EC, Dietmaier, W, Baselga, E, Parera, E, Vicente, A, Casanova, A, Cigudosa, J, Mentzel, T, Pujol, RM, Landthaler, M, Real, FX
Publicada:
1 abr 2012
Resumen:
Background Activating RAS mutations in the germline cause rare developmental disorders such as Costello syndrome. Somatic RAS mutations are found in approximately 30% of human cancers. Keratinocytic epidermal nevi (KEN) represent benign congenital skin lesions arranged along Blaschko's lines. A subgroup of KEN is caused by hotspot oncogenic FGFR3 and PIK3CA mutations in mosaicism, but the majority lack these mutations.
Methods This study screened 72 KEN for activating mutations in RAS genes and other oncogenes.
Results Activating RAS mutations were identified in 28/72 (39%) of KEN. HRAS was the most commonly affected oncogene (86%), with the HRAS p.G13R substitution representing a new hotspot mutation.
Conclusion These results indicate that activating RAS somatic mutations leading to mosaicism result in benign KEN of the skin. Given the prevalence of KEN, mosaic HRAS mutations appear to be more common in patients than germline ones. These findings identify KEN as a mosaic RASopathy and lend further support to the notion that genetic mosaicism is an important contributor to disease.
Filiaciones:
Hafner, C:
Univ Regensburg, Dept Dermatol, D-93053 Regensburg, Germany
Toll, A:
Univ Autonoma Barcelona, Serv Dermatol, Hosp Mar Parc Salut Mar, E-08193 Barcelona, Spain
Gantner, S:
Univ Regensburg, Dept Dermatol, D-93053 Regensburg, Germany
Mauerer, A:
Univ Regensburg, Dept Dermatol, D-93053 Regensburg, Germany
Lurkin, I:
Erasmus MC, Dept Pathol, Josephine Nefkens Inst, Rotterdam, Netherlands
Acquadro, F:
Ctr Nacl Invest Oncol, Programa Genet Canc Humano, Grp Citogenet Mol, Madrid, Spain
Ctr Nacl Invest Oncol, Programa Genet Canc Humano, CIBERER, Madrid, Spain
Fernandez-Casado, A:
Univ Autonoma Barcelona, Serv Dermatol, Hosp Mar Parc Salut Mar, E-08193 Barcelona, Spain
Zwarthoff, EC:
Erasmus MC, Dept Pathol, Josephine Nefkens Inst, Rotterdam, Netherlands
Dietmaier, W:
Univ Regensburg, Inst Pathol, Regensburg, Germany
Baselga, E:
Hosp Santa Creu & Sant Pau, Dept Dermatol, Barcelona, Spain
Parera, E:
Univ Autonoma Barcelona, Serv Dermatol, Hosp Mar Parc Salut Mar, E-08193 Barcelona, Spain
Vicente, A:
Univ Barcelona, Hosp St Joan de Deu, Dept Dermatol, E-08007 Barcelona, Spain
Casanova, A:
Ctr Nacl Invest Oncol, Programa Patol Mol, Grp Carcinogenesis Epitelial, Madrid, Spain
Cigudosa, J:
Ctr Nacl Invest Oncol, Programa Genet Canc Humano, Grp Citogenet Mol, Madrid, Spain
Ctr Nacl Invest Oncol, Programa Genet Canc Humano, CIBERER, Madrid, Spain
Pujol, RM:
Univ Autonoma Barcelona, Serv Dermatol, Hosp Mar Parc Salut Mar, E-08193 Barcelona, Spain
Landthaler, M:
Univ Regensburg, Dept Dermatol, D-93053 Regensburg, Germany
Real, FX:
Ctr Nacl Invest Oncol, Programa Patol Mol, Grp Carcinogenesis Epitelial, Madrid, Spain
Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain
Open Access
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