Hafner C, Stoehr R, van Oers J M M, Zwarthoff E C, Hofstaedter F, Landthaler M, Hartmann A, Vogt T
Department of Dermatology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany.
Br J Dermatol. 2009 Mar;160(3):546-51. doi: 10.1111/j.1365-2133.2008.08963.x. Epub 2008 Dec 12.
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.
To analyse SL for potential FGFR3 and PIK3CA mutations.
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.
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.
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.
日光性雀斑（SL）是常见的良性皮肤病变，尤其多见于老年人的阳光暴露部位，因此是（光）老化皮肤的一个标志。有人提出SL可能随后演变为腺样脂溢性角化病（SK）。然而，关于SL的遗传基础知之甚少。在人类SK中，最近已鉴定出FGFR3和PIK3CA突变。
分析SL中潜在的FGFR3和PIK3CA突变。
我们使用SNaPshot多重分析法筛选30个SL中的FGFR3突变。对于PIK3CA突变，我们采用外显子9直接测序和H1047R热点突变（外显子20）的SNaPshot分析法。由于补骨脂素加紫外线A（PUVA）雀斑显示V600E BRAF热点突变，我们还通过等位基因特异性聚合酶链反应在SL中研究了该突变。
在30个SL中的5个（17%）检测到FGFR3突变，在28个SL中的2个（7%）检测到PIK3CA突变。可用于BRAF分析的28个SL中均未发现V600E突变。
我们的结果表明FGFR3和PIK3CA突变参与了SL的发病机制。这些突变在SL和SK中的出现提示存在共同的遗传基础。我们的发现进一步证实了先前的推测，即紫外线暴露可能是人类皮肤中FGFR3和PIK3CA突变的一个致病因素。
