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


METHODS
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 rhabdomyosarcoma but not in the dermal component of the EN lesion or in unaffected tissues, including normal skin or blood.


CONCLUSIONS
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.
Bourdeaut
Franck
F
CHU Nantes, Service d'oncologie pédiatrique, Nantes, France.
Hérault
Aurélie
A
Gentien
David
D
Pierron
Gaëlle
G
Ballet
Stelly
S
Reynaud
Stéphanie
S
Paris
Régine
R
Schleiermacher
Gudrun
G
Baumann
Clarisse
C
Philippe-Chomette
Pascale
P
Gauthier-Villars
Marion
M
Peuchmaur
Michel
M
Radvanyi
François
F
Delattre
Olivier
O
D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D009030:Mosaicism; D009154:Mutation / Q000235:genetics*; D054000:Nevus, Sebaceous of Jadassohn / Q000150:complications / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D007690:Polycystic Kidney Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012208:Rhabdomyosarcoma / Q000150:complications / Q000235:genetics* / Q000473:pathology; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins