HG-01: A NOVEL GENODERMATOSIS SYNDROME INDUCED BY SOMATIC BRAF V600E MOSAICISM, COMPRISING CONGENITAL ANAPLASTIC ASTROCYTOMA AND LINEAR SYRINGOCYSTADENOMA PAPILLIFERUM

Genodermatoses are occasionally caused by genetic mosaicism for some somatic mutations, a part of which are complicated with extra-cutaneous abnormalities. Here we report an infant with congenital anaplastic astrocytoma, linear syringocystadenoma papilliferum and ocular abnormalities. Interestingly, the BRAF V600E mutation was detected in both brain and skin tumor cells, but not in blood or normal skin cells, suggesting the somatic mosaicism for the mutation. Of note, HRAS and KRAS genes were wild-type in all specimens. Clinically, the brain tumor gradually became life-threatening without any response to conventional chemotherapies including carboplatin, etoposide and temozolomide. Vemurafenib, a BRAF V600E inhibitor, was administered daily after the detection of the BRAF mutation. This single-agent therapy was dramatically effective on the anaplastic astrocytoma; the tumor regressed, cerebrospinal fluid cell count and protein levels decreased to normal, and hydrocephalus resolved. Moreover, other lesions including skin tumor and corneal cyst also responded to vemurafenib. The tumor keeps shrinking after 6 months of the treatment. We present a genodermatosis syndrome associated with the BRAF V600E mosaicism, that is better stated as a new entity in the mosaic RASopathies, partly overlapping with the Schimmelpenning syndrome which is driven by the mosaicism for HRAS and/or KRAS mutations. Screening for BRAF V600E is especially useful for those with malignant tumors, for it is one of the best druggable targets.