FGFR3 and PIK3CA mutations are involved in the molecular pathogenesis of solar lentigo.
BACKGROUND
Solar lentigines (SL) are frequent benign skin lesions appearing on sun-exposed areas especially in elderly people and therefore represent a hallmark of (photo)aged skin. It has been proposed that SL may subsequently evolve into adenoid seborrhoeic keratosis (SK). However, little is known about the genetic basis of SL. In human SK, FGFR3 and PIK3CA mutations have recently been identified.


OBJECTIVE
To analyse SL for potential FGFR3 and PIK3CA mutations.


METHODS
We screened 30 SL for FGFR3 mutations using a SNaPshot multiplex assay. For PIK3CA mutations we used direct sequencing of exon 9 and a SNaPshot assay for the H1047R hotspot mutation (exon 20). Because psoralen plus ultraviolet A (PUVA) lentigines show the V600E BRAF hotspot mutation, we additionally investigated this mutation in SL by allele-specific polymerase chain reaction.


RESULTS
FGFR3 mutations were detected in five of 30 (17%) SL and PIK3CA mutations in two of 28 (7%) SL. None of 28 SL available for BRAF analysis revealed the V600E mutation.


CONCLUSIONS
Our results suggest that FGFR3 and PIK3CA mutations are involved in the pathogenesis of SL. The occurrence of these mutations in both SL and SK suggests a common genetic basis. Our findings furthermore substantiate previous speculations that UV exposure may be a causative factor for FGFR3 and PIK3CA mutations in human skin.
Hafner
C
C
Department of Dermatology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany. christian.hafner@klinik.uni-regensburg.de
Stoehr
R
R
van Oers
J M M
JM
Zwarthoff
E C
EC
Hofstaedter
F
F
Landthaler
M
M
Hartmann
A
A
Vogt
T
T
D000328:Adult; D000368:Aged; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D007911:Lentigo / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D010787:Photosensitivity Disorders / Q000235:genetics* / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D015595:Skin Aging / Q000235:genetics
D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf