Somatic BRAF c.1799T>A p.V600E Mosaicism syndrome characterized by a linear syringocystadenoma papilliferum, anaplastic astrocytoma, and ocular abnormalities.
Somatic BRAF c.1799T>A p.V600E Mosaicism syndrome characterized by a linear syringocystadenoma papilliferum, anaplastic astrocytoma, and ocular abnormalities.
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体细胞 BRAF c.1799T>A p.V600E 镶嵌综合征，其特征为线性乳头状汗管囊腺瘤、间变性星形细胞瘤和眼部异常。
DOI：
10.1002/ajmg.a.37376
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Kure S.
中科院分区：
文献类型：
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作者：
Watanabe Y;Shido K;Niihori T;Niizuma H;Katata Y;Iizuka C;Oba D;Moriya K;Saito-Nanjo Y;Onuma M;Rikiishi T;Sasahara Y;Watanabe M;Aiba S;Saito R;Sonoda Y;Tominaga T;Aoki Y;Kure S.
癌基因体细胞突变的遗传镶嵌现象在遗传性皮肤病中很常见，可并发皮肤外异常。我们在此报告一位患有先天性间变性星形细胞瘤、线状淋巴管囊腺瘤及眼部异常的婴儿。TheBRAFc。p.V600E突变在脑和皮肤肿瘤细胞中均检测到，但在血液和正常皮肤细胞中未检测到，提示该突变存在体细胞嵌合性。临床上，脑肿瘤逐渐危及生命，对卡铂、依托泊苷、替莫唑胺等常规化疗无反应。Vemurafenib是一种BRAF p.V600E抑制剂，在检测到BRAF突变后每天给药。这种单药治疗对间变性星形细胞瘤显著有效；肿瘤消退，脑脊液细胞计数和蛋白水平降至正常水平，脑积水消退。此外，包括角膜囊肿在内的其他病变也对vemurafenib有反应。治疗6个月后，脑肿瘤继续缩小。我们提出一种与brafc相关的遗传性皮肤病综合征。1799T>A p.V600E马赛克。该综合征可能代表了马赛克RASopathies中的一个新实体，部分与Schimmelpenning - Feuerstein - Mims综合征重叠，后者是由hrasand /或kras活化突变的马赛克驱动的。筛选forBRAFc。A p.V600E对恶性肿瘤患者特别有用，因为它是最具药物活性的靶点之一。©2015 Wiley期刊公司
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. TheBRAFc.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 theBRAFmutation. 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 withBRAFc.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 ofHRASand/orKRASactivating mutations. Screening forBRAFc.1799T>A p.V600E is especially useful for those with malignant tumors, because it is one of the most‐druggable targets. © 2015 Wiley Periodicals, Inc.