Mosaicism for oncogenic G12D KRAS mutation associated with epidermal nevus, polycyctic kidneys and rhabdomyosarcoma

Olivier Delattre (1)

1 Institut Curie [Paris]

Epidermal nevus (EN) is a congenital disorder characterized by hyperpigmented epidermal thickening following a Blashko's line. It is due to somatic mutations in either FGFR3 or PI3KCA in half of cases, and remains of unknown genetic origin in the other half. EN is also observed as part of complex developmental disorders or in association with bladder carcinomas, also related to FGFR3 and PI3KCA mutations. Hence, mosaic mutations of these genes have been suggested and occasionally evidenced in syndromic EN. In this report, we describe the co-occurrence of EN, rhabdomyosarcoma, polycystic kidneys and growth failure in an infant. An oncogenic G12D KRAS mutation was detected in both the epidermal component of the EN and in the rhabodmyosarcoma but neither in the dermal component of the EN lesion nor in unaffected tissues including normal skin or blood. This report identifies for the first time that a KRAS mutation in epiderma causes EN. The 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 oncogenes mutations in childhood cancers.

Mots clés: Dermatology; Genetics; Paediatric oncology

Olivier Delattre. Mosaicism for oncogenic G12D KRAS mutation associated with epidermal nevus, polycyctic kidneys and rhabdomyosarcoma. Journal of Medical Genetics, 2010, 47 (12), pp.859. ⟨10.1136/jmg.2009.075374⟩. ⟨hal-00560777⟩