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Hafner, Christian; López-Knowles, Elena; Luis, Nuno M.; Toll, Agustí; Baselga, Eulàlia; Fernández-Casado, Alex; Hernández, Silvia; Ribé, Adriana; Mentzel, Thomas; Stoehr, Robert; Hofstaedter, Ferdinand; Landthaler, Michael; Vogt, Thomas; Pujol, Ramòn M.; Hartmann, Arndt; Real, Francisco X.

Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern

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  • Medientyp: E-Artikel
  • Titel: Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern
  • Beteiligte: Hafner, Christian; López-Knowles, Elena; Luis, Nuno M.; Toll, Agustí; Baselga, Eulàlia; Fernández-Casado, Alex; Hernández, Silvia; Ribé, Adriana; Mentzel, Thomas; Stoehr, Robert; Hofstaedter, Ferdinand; Landthaler, Michael; Vogt, Thomas; Pujol, Ramòn M.; Hartmann, Arndt; Real, Francisco X.
  • Erschienen: Proceedings of the National Academy of Sciences, 2007
  • Erschienen in: Proceedings of the National Academy of Sciences
  • Sprache: Englisch
  • DOI: 10.1073/pnas.0705218104
  • ISSN: 0027-8424; 1091-6490
  • Schlagwörter: Multidisciplinary
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p> Activating mutations of the p110 α subunit of PI3K ( <jats:italic>PIK3CA</jats:italic> ) oncogene have been identified in a broad spectrum of malignant tumors. However, their role in benign or preneoplastic conditions is unknown. Activating FGF receptor 3 ( <jats:italic>FGFR3</jats:italic> ) mutations are common in benign skin lesions, either as embryonic mutations in epidermal nevi (EN) or as somatic mutations in seborrheic keratoses (SK). <jats:italic>FGFR3</jats:italic> mutations are also common in low-grade malignant bladder tumors, where they often occur in association with <jats:italic>PIK3CA</jats:italic> mutations. Therefore, we examined exons 9 and 20 of <jats:italic>PIK3CA</jats:italic> and <jats:italic>FGFR3</jats:italic> hotspot mutations in EN ( <jats:italic>n</jats:italic> = 33) and SK ( <jats:italic>n</jats:italic> = 62), two proliferative skin lesions lacking malignant potential. Nine of 33 (27%) EN harbored <jats:italic>PIK3CA</jats:italic> mutations; all cases showed the E545G substitution, which is uncommon in cancers. In EN, R248C was the only <jats:italic>FGFR3</jats:italic> mutation identified. By contrast, 10 of 62 (16%) SK revealed the typical cancer-associated <jats:italic>PIK3CA</jats:italic> mutations E542K, E545K, and H1047R. The same lesions displayed a wide range of <jats:italic>FGFR3</jats:italic> mutations. Corresponding unaffected tissue was available for four EN and two mutant SK: all control samples displayed a WT sequence, confirming the somatic nature of the mutations found in lesional tissue. Forty of 95 (42%) lesions showed at least one mutation in either gene. <jats:italic>PIK3CA</jats:italic> and <jats:italic>FGFR3</jats:italic> mutations displayed an independent distribution; 5/95 lesions harbored mutations in both genes. Our findings suggest that, in addition to their role in cancer, oncogenic <jats:italic>PIK3CA</jats:italic> mutations contribute to the pathogenesis of skin tumors lacking malignant potential. The remarkable genotype–phenotype correlation as observed in this study points to a distinct etiopathogenesis of the mutations in keratinocytes occuring either during fetal development or in adult life. </jats:p>
  • Zugangsstatus: Freier Zugang