Identification of novel fibroblast growth factor receptor 3 gene mutations in actinic cheilitis and squamous cell carcinoma of the lip.

Objective: Activating mutations in the fibroblast growth factor receptor 3 (FGFR3) gene are responsible for several craniosynostosis and chondrodysplasia syndromes as well as some human cancers, including bladder and cervical carcinoma. Despite a high frequency in some benign skin disorders, FGFR3 mutations have not been reported in cutaneous malignancies. Actinic cheilitis (AC) is a sun-induced premalignancy affecting the lower lip that frequently progresses to squamous cell carcinoma (SCC). The objective of this study was to determine if FGFR3 gene mutations are present in AC and SCC of the lip.

Study Design: DNA was extracted and purified from microdissected, formalin-fixed, paraffin-embedded tissue sections of 20 cases of AC and SCC arising in AC. Exons 7, 15, and 17 were PCR amplified and direct sequenced.

Results: Four novel somatic mutations in the FGFR3 gene were identified: exon 7 mutation 742C-->T (amino acid change R248C), exon 15 mutations 1850A-->G (D617G) and 1888G-->A (V630M), and exon 17 mutation 2056G-->A (E686K). Grade of dysplasia did not correlate with presence of mutations.

Conclusion: The frequency of FGFR3 receptor mutations suggests a functional role for the FGFR3 receptor in the development of epithelial disorders, and perhaps this change may contribute to the pathogenesis of some AC and SCC.