Mosaicism for oncogenic G12D KRAS mutation associated with epidermal nevus, polycystic kidneys and rhabdomyosarcoma. Issue 12 (30th August 2010)

• Record Type: Journal Article
• Authors: Bourdeaut, Franck; Hérault, Aurélie; Gentien, David; Pierron, Gaëlle; Ballet, Stelly; Reynaud, Stéphanie; Paris, Régine; Schleiermacher, Gudrun; Baumann, Clarisse; Philippe-Chomette, Pascale; Gauthier-Villars, Marion; Peuchmaur, Michel; Radvanyi, François; Delattre, Olivier
• Is Part Of: Journal of medical genetics. Volume 47:Issue 12(2010)
• Page Start: 859
• Page End: 862
• Publication Date: 2010-08-30
• Subjects: Mosaicism -- KRAS -- rhabdomyosarcoma -- epidermal nevus -- dermatology -- genetics -- paediatric oncology; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.2009.075374
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Background: Epidermal nevus (EN) is a congenital disorder characterised by hyperpigmented epidermal thickening following a Blaschko's line. It is due to somatic mutations in either FGFR3 or PIK3CA in half of the cases, and remains of unknown genetic origin in the other half. EN is also seen as part of complex developmental disorders or in association with bladder carcinomas, also related to FGFR3 and PIK3CA mutations. Mosaic mutations of these genes have been occasionally found in syndromic EN. Case report: The co-occurrence of EN, rhabdomyosarcoma, polycystic kidneys and growth retardation in an infant is described. Results: An oncogenic G12D KRAS mutation was detected in both the epidermal component of the EN and in the rhabodmyosarcoma but not in the dermal component of the EN lesion or in unaffected tissues, including normal skin or blood. Conclusion: This report shows for the first time that a KRAS mutation in epiderma causes EN. Observation of the same G12D KRAS mutation in two distinct regions of the body strongly suggests a somatic mosaicism. Finally, this report highlights the potentially underestimated importance of mosaic oncogene mutations in childhood cancers.