BRAF mutations are common somatic events in melanocytic nevi
BRAF mutations are common somatic events in melanocytic nevi
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DOI：
10.1046/j.0022-202x.2004.22225.x
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发表时间：
2004-02-01
影响因子：
6.5
通讯作者：
Hemminki, K
中科院分区：
文献类型：
--
作者：
Kumar, R;Angelini, S;Hemminki, K
我们确定了BRAF，N-ras和CDKN 2A基因在27个组织学上不同的黑色素细胞痣和相应的周围组织从17个人的突变。BRAF和N-ras基因突变在16个个体（94%）的22个痣（81%）中被发现。在18例痣中检测到主要的BRAF突变T1799 A（V600 E），1例痣在同一基因中有一个新的A1781 G（D594 V）突变，3例痣在N-ras基因的密码子61处有突变。4例患者的两个痣都携带BRAF突变，而另外2例患者的1个痣显示BRAF突变，第二个痣有N-ras突变。在2例远离痣的正常皮肤中显示BRAF突变。在CDKN 2A基因中未检测到突变。在这项研究中，BRAF和N-ras基因的突变与痣的组织学类型、位置、皮肤类型、大小或数量无关。我们的研究结果表明，突变的BRAF基因，并在一定程度上在N-ras基因代表早期的体细胞事件发生在黑素细胞痣。我们假设太阳紫外线照射对黑色素瘤的双重影响，通过诱变和增加黑色素细胞痣的数量，其中许多携带BRAF或N-ras突变。
We determined mutations in the BRAF, N-ras, and CDKN2A genes in 27 histologically diverse melanocytic nevi and corresponding surrounding tissues from 17 individuals. Mutations in the BRAF and N-ras gene were found in 22 nevi (81%) from 16 individuals (94%). The predominant BRAF mutation T1799A (V600E) was detected in 18 nevi; 1 nevus had a novel A1781G (D594V) mutation in the same gene and 3 nevi had mutations in codon 61 of the N-ras gene. In 4 individuals both nevi carried a BRAF mutation, whereas in 2 other individuals 1 nevus showed a BRAF mutation and the second nevus had an N-ras mutation. In 2 individuals normal skin distant from nevi showed a BRAF mutation. No mutations were detected in the CDKN2A gene. The mutations in the BRAF and N-ras genes, in this study, were not associated with histologic type, location, skin type, size, or numbers of nevi. Our results suggest that mutations in the BRAF gene and to some extent in the N-ras gene represent early somatic events that occur in melanocytic nevi. We hypothesize the dual effect of solar ultraviolet irradiation on melanoma, through mutagenesis and by increasing the number of melanocytic nevi, many of which carry a BRAF or N-ras mutation.