Georgieva Ivelina A, Mauerer Andreas, Groesser Leopold, Herschberger Eva, Aslanidis Charalampos, Dietmaier Wolfgang, Landthaler Michael, Hafner Christian
*Department of Dermatology, University of Regensburg, Regensburg, Germany; †Department of Dermatology, Venereology, and Allergology, University Medical Center Mannheim, Ruprecht-Karl-University of Heidelberg, Mannheim, Germany; ‡Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany; and §Molecular Pathology Diagnostic Unit, Institute of Pathology, University of Regensburg, Regensburg, Germany.
Am J Dermatopathol. 2014 Aug;36(8):635-42. doi: 10.1097/DAD.0b013e31828c0542.
Seborrheic keratosis (SK) represents a frequent epidermal skin tumor. Although lacking a malignant potential, these tumors reveal multiple oncogenic mutations. A previous study identified activating mutations in 89% of SK, particularly in FGFR3 and PIK3CA genes. The aim of this study was to identify further oncogenic mutations in human SK. Therefore, we screened for mutations in EGFR, FGFR2, PIK3R1, HRAS, KRAS, and NRAS genes using both Sanger sequencing of selected exons and a multiplex SNaPshot assay in 58 SK of 14 patients. We identified a somatic EGFR p.L858R mutation in 1 SK. Furthermore, the HRAS mutations p.G13R (2/58 SK) and p.Q61L (2/58 SK) were found. These mutations have not been described in human SK yet. In addition, 1 SK revealed the KRAS p.G12V mutation, which has already been reported in SK. No mutations were detected in FGFR2, PIK3R1, and NRAS genes. The results of this study suggest that activating mutations of EGFR, HRAS, and KRAS contribute to the pathogenesis of human SK, although at a lower frequency than FGFR3 and PIK3CA mutations. FGFR2, PIK3R1, and NRAS mutations obviously do not have a significant role in the development of SK.
脂溢性角化病（SK）是一种常见的表皮皮肤肿瘤。尽管这些肿瘤没有恶性潜能，但却显示出多种致癌突变。先前的一项研究发现，89%的SK存在激活突变，尤其是在FGFR3和PIK3CA基因中。本研究的目的是确定人类SK中更多的致癌突变。因此，我们使用选定外显子的桑格测序法和多重SNaPshot分析法，对14例患者的58个SK样本中的EGFR、FGFR2、PIK3R1、HRAS、KRAS和NRAS基因进行了突变筛查。我们在1个SK样本中鉴定出一个体细胞EGFR p.L858R突变。此外，还发现了HRAS突变p.G13R（2/58个SK样本）和p.Q61L（2/58个SK样本）。这些突变在人类SK中尚未有过描述。另外，1个SK样本显示出KRAS p.G12V突变，该突变在SK中已有报道。在FGFR2、PIK3R1和NRAS基因中未检测到突变。本研究结果表明，EGFR、HRAS和KRAS的激活突变虽然频率低于FGFR3和PIK3CA突变，但对人类SK的发病机制有一定作用。FGFR-2、PIK3R1和NRAS突变显然在SK的发生发展中没有显著作用。
