BRAF mutations in melanocytic tumors (nevi and melanomas) from organ transplant recipients.

BRAF is a gene of the RAF family of kinases, frequently mutated in benign and malignant melanocytic tumors (nevi and melanomas). Organ transplant recipients are at high risk for developing various tumors, including melanocytic ones. We studied a group of 129 melanocytic tumors including various subtypes of nevi (n: 114) and melanomas (n: 15) excised from transplant (n: 63) and control (non-immunosuppressed) patients (n: 66) as to BRAF mutation status. Mutation research was performed after extraction of DNA from archival material (paraffin-embedded tissue specimens) by sequence analysis. BRAFV600E accounted for the most prevalent mutation found (94%). Melanocytic tumors from transplant patients had a lower frequency of BRAF mutations than control lesions (45.4% vs 63.5%, p<.05). The explanation for this difference is currently unknown. The possibility exists that in transplant patients, factors linked to immunosuppression (most likely immunosuppressive drugs) induce additional mutations, or activate alternative signaling pathways, which compensates for the lower rate of activating BRAF mutations in tumors developing in these patients.