FGFR3, PIK3CA and RAS mutations in benign lichenoid keratosis.

Area of Science:

• Dermatology
• Molecular Genetics
• Oncology

Background:

• Benign lichenoid keratoses (BLKs) are skin lesions potentially representing regressive forms of epidermal tumors.
• The genetic underpinnings of BLKs remain largely unknown.
• Previous research linked specific mutations to related epidermal tumors like solar lentigo and seborrheic keratosis.

Purpose of the Study:

• To investigate the presence of FGFR3, PIK3CA, and RAS mutations in BLKs.
• To determine if these mutations contribute to the pathogenesis of BLKs.
• To explore the relationship between BLKs and other benign epidermal tumors on a molecular level.

Main Methods:

• Manual microdissection and DNA isolation from 52 BLK samples.
• Screening for hotspot mutations in FGFR3, PIK3CA, and RAS genes using SNaPshot multiplex assays.
• Analysis of control tissues and lichen planus samples to confirm mutation specificity and somatic nature.

Main Results:

• Mutations were identified in 12% (FGFR3), 19% (PIK3CA), 12% (HRAS), and 4% (KRAS) of BLKs.
• FGFR3 and RAS mutations were mutually exclusive; one case showed co-occurring PIK3CA and HRAS mutations.
• Somatic mutations were confirmed in nine BLKs, with no mutations found in adjacent normal tissue or lichen planus samples.

Conclusions:

• Approximately 50% of BLKs harbor FGFR3, PIK3CA, or RAS mutations.
• These genetic findings support the hypothesis that BLKs represent regressive variants of benign epidermal tumors.
• The study provides molecular genetic evidence linking BLKs to seborrheic keratosis and solar lentigo.