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 rhabdomyosarcoma 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.
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 G12DKRAS 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. CONCLUSION: This report shows for the first time that a KRAS mutation in epiderma causes EN. Observation of the same G12DKRAS 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.
Authors: Leopold Groesser; Eva Herschberger; Arno Ruetten; Claudia Ruivenkamp; Enrico Lopriore; Markus Zutt; Thomas Langmann; Sebastian Singer; Laura Klingseisen; Wulf Schneider-Brachert; Agusti Toll; Francisco X Real; Michael Landthaler; Christian Hafner Journal: Nat Genet Date: 2012-06-10 Impact factor: 38.330
Authors: Samantha N McNulty; Michael J Evenson; Meagan M Corliss; Latisha D Love-Gregory; Molly C Schroeder; Yang Cao; Yi-Shan Lee; Beth A Drolet; Julie A Neidich; Catherine E Cottrell; Jonathan W Heusel Journal: Am J Hum Genet Date: 2019-10-03 Impact factor: 11.025
Authors: Michael J McConnell; John V Moran; Alexej Abyzov; Schahram Akbarian; Taejeong Bae; Isidro Cortes-Ciriano; Jennifer A Erwin; Liana Fasching; Diane A Flasch; Donald Freed; Javier Ganz; Andrew E Jaffe; Kenneth Y Kwan; Minseok Kwon; Michael A Lodato; Ryan E Mills; Apua C M Paquola; Rachel E Rodin; Chaggai Rosenbluh; Nenad Sestan; Maxwell A Sherman; Joo Heon Shin; Saera Song; Richard E Straub; Jeremy Thorpe; Daniel R Weinberger; Alexander E Urban; Bo Zhou; Fred H Gage; Thomas Lehner; Geetha Senthil; Christopher A Walsh; Andrew Chess; Eric Courchesne; Joseph G Gleeson; Jeffrey M Kidd; Peter J Park; Jonathan Pevsner; Flora M Vaccarino Journal: Science Date: 2017-04-27 Impact factor: 47.728
Authors: Janet Y Li; Michael F Berger; Ashfaq Marghoob; Umesh K Bhanot; Jennifer P Toyohara; Melissa P Pulitzer Journal: J Cutan Pathol Date: 2014-07-09 Impact factor: 1.587