Somatic FGFR3Mutations In Seborrheic Keratosis And Acanthosis Nigricans Of Chinese Patients

Background:In skin tissue, FGFR3germline mutations exist in many syndromes with acanthosis nigricans, somatic mutations exist in seborrheic keratosis.Maybe two kinds of skin diseases have a shared genetic pathway. Before studying human skin disease of FGFR3somatic mutations, a lot of malignant tumor of somatic mutation has been studied, such as multiple myeloma and prostate cancer, colorectal cancer, cervical cancer, bladder cancer and so on. In bone disease and most studied tumor, there are11activating mutations in exon7,10,15of FGFR3:c.742c> T(R248C), c.746c(S249C)> G, c.1114G>T (G372C), c.1117A> T (S373C), c. c.1124A> G (Y375C),1144G> A (G382R), c.1178c> A(A393E), c. c.1850A> G(D617G),1888G> A (V630M), c.1954A> G (K652E), c.1955A> T (K652M)Objective:To detect FGFR3somatic mutations of seborrheic keratosis and acanthosis nigricans in Chinese han populationMethods:Genomic DNA was extracted from the peripheral paraffin-embedded tissues using the QIAamp DNA FFPE Tissue Kit (QIAGEN, Hilden, Germany). Using polymerase chain reaction (PCR), the SnapShot technology, Sanger sequencing technology of48cases of seborrheic keratosis,30patients of acanthosis nigricans,and18cases of normal skin tissues to detect11activating mutations in exon7,10,15of FGFR3and19exons of FGFR3.The11activating mutations covered all yet identified FGFR3mutations in benign acanthotic skin tumors(seborrheic keratoses, epidermal nevi) and urothelial carcinoma. Results:1SnapShot technology:FGFR3mutations were found in20of48SKs(42%),while28of48(58%) revealed a wild-type status at the investigated loci. However,two ANs revealed G382R mutation of FGFR3.This is the first report of FGFR3mutations in AN.2. Sanger sequencing technology:Sanger sequencing is the gold standard in SNP genotyping. To guarantee the reliability and rigor of the results, we tested exon7、10、15of FGFR3, which consistent with the SnapShot technology testing.Conclusion:We identified five reported mutations in SK and one novel mutation in AN.Our findings provided an addition to the FGFR3mutation database and will contribute further to the understanding to the pathogenesis of benign skin tumors. As specific inhibitors of FGFR3are already available,topical treatment with inhibitors of FGFR3may represent a promising new non-invasive therapy option in the treatment.