title: Somatic BRAF c.1799T>A p.V600E Mosaicism syndrome characterized by a linear syringocystadenoma papilliferum, anaplastic astrocytoma, and ocular abnormalities.
abstract: Genetic mosaicism for somatic mutations of oncogenes is common in genodermatoses, which can be complicated with extra-cutaneous abnormalities. Here we describe an infant with a congenital anaplastic astrocytoma, a linear syringocystadenoma papilliferum, and ocular abnormalities. The BRAF c.1799T>A p.V600E mutation was detected in both the brain and skin tumor cells but not in the blood or normal skin cells, suggesting somatic mosaicsism for the mutation. Clinically, the brain tumor gradually became life threatening without any response to conventional chemotherapies including carboplatin, etoposide, and temozolomide. Vemurafenib, a BRAF p.V600E inhibitor, was administered daily after the detection of the BRAF mutation. This single-agent therapy was dramatically effective against the anaplastic astrocytoma; the tumor regressed, the cerebrospinal fluid cell count and protein levels decreased to normal levels, and hydrocephalus resolved. Moreover, other lesions including a corneal cyst also responded to vemurafenib. The brain tumor continued shrinking after 6 months of treatment. We present a genodermatosis syndrome associated with BRAF c.1799T>A p.V600E mosaicism. This syndrome may represent a new entity in the mosaic RASopathies, partly overlapping with Schimmelpenning-Feuerstein-Mims syndrome, which is driven by mosaicism of HRAS and/or KRAS activating mutations. Screening for BRAF c.1799T>A p.V600E is especially useful for those with malignant tumors, because it is one of the most-druggable targets.
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Dermatology, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Shido
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Niihori
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Niizuma
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Katata
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Iizuka
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Daiju
authors.initials: D
authors.lastname: Oba
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Moriya
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Saito-Nanjo
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Masaei
authors.initials: M
authors.lastname: Onuma
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Rikiishi
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Sasahara
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Dermatology, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Setsuya
authors.initials: S
authors.lastname: Aiba
authors.affiliation: Department of Neurosurgery, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Saito
authors.affiliation: Department of Neurosurgery, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sonoda
authors.affiliation: Department of Neurosurgery, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Teiji
authors.initials: T
authors.lastname: Tominaga
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
mesh_terms: D006607:Adenoma, Sweat Gland / Q000188:drug therapy / Q000235:genetics*; D001254:Astrocytoma / Q000188:drug therapy / Q000235:genetics*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics*; D005123:Eye / Q000473:pathology; D005124:Eye Abnormalities / Q000235:genetics; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007223:Infant; D009030:Mosaicism; D054000:Nevus, Sebaceous of Jadassohn / Q000235:genetics; D047928:Premature Birth; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D013449:Sulfonamides / Q000627:therapeutic use; D013544:Sweat Gland Neoplasms / Q000188:drug therapy / Q000235:genetics*; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF c.1799T>A p.V600E; Schimmelpenning-Feuerstein-Mims syndrome; anaplastic astrocytoma; vemurafenib