The incidence of keratinocyte carcinomas is increasing worldwide and currently there is no standardised strategy for the follow-up of patients with multiple tumours.,The objective of this study was to assess the prevalence of premalignant lesions, i.e., actinic keratosis and Bowen’s disease, as well as basal cell carcinoma (BCC) and cutaneous melanoma (CM) among patients with cutaneous squamous cell carcinoma (cSCC).,Pathology database search was performed to identify all cSCC patients diagnosed in the Pirkanmaa region of Finland in 2006-2015.,Details of the patients and tumours were obtained through medical record review.,The cohort consisted of 774 patients with 1131 cSCC tumours.,Overall 559 patients (72%) had premalignant lesions.,A total of 316 patients (41%) had BCC and 52% of these (n = 164) had more than one BCC tumour. 50 patients (6%) had CM.,Overall 180 cSCC patients (23%) had no premalignant changes, BCC or CM.,The median age of these patients was 6 years less than that of the patients with premalignant lesions (p < 0.001) or BCC (p < 0.001).,The invasion depth of the tumours was deeper in the patients with only cSCC (median 3 mm, interquartile range 2-6) than in those with premalignant lesions or BCC (median 2 mm, interquartile range 1-3), p < 0.001.,CSCC patients have a high risk of developing multiple skin cancers and need long-term follow-up.
Cutaneous squamous cell carcinoma (cSCC) differs from SCC of other organs in its strong association with chronic sun exposure.,However, the specific driver mutations in cSCC remain unknown.,Fusion genes in established cSCC cell lines (A431 and DJM-1) were predicted by transcriptome sequence, and validated by Sanger sequence, fluorescence in situ hybridization and G-banding.,By transcriptome sequencing, we identified fusion gene EGFR-PPARGC1A in A431, which were expressed in 31 of 102 cSCCs.,The lesions harboring the fusion gene tended to be located in sun-exposed areas.,In vivo cutaneous implantation of EGFR-PPARGC1A-expressing NIH3T3 induced tumors resembling human cSCC, indicating its potent tumorigenicity.,NIH3T3 transfected with EGFR-PPARGC1A as well as A431 showed increased cell proliferation activity.,With regard to underlying mechanism, EGFR-PPARGC1A protein causes constitutive tyrosine phosphorylation, and induces the phosphorylation of wild-type full-length epidermal growth factor receptor (EGFR) by dimerization.,Conversely, the RNAi-mediated attenuation of EGFR or CRISPR/Cas9-mediated knockdown of the fusion gene in A431 led to a decrease in the cell number, and may have therapeutic value.,Our findings advance the knowledge concerning genetic causes of cSCC and the function of EGFR, with potential implications for new diagnostic and therapeutic approaches.