High BRAF mutation frequency does not characterize all melanocytic tumor types
High BRAF mutation frequency does not characterize all melanocytic tumor types
复制标题
DOI：
10.1002/ijc.20325
复制
发表时间：
2004-09-20
影响因子：
6.4
通讯作者：
Pringle, JH
中科院分区：
文献类型：
--
作者：
Saldanha, G;Purnell, D;Pringle, JH
皮肤黑色素瘤（CM）是最致命的皮肤癌。沿着一些良性黑素细胞肿瘤，大多数显示BRAF或NRAS突变，但尚不清楚这些突变是否是所有形式的黑素细胞瘤形成所必需的。我们筛选了79个不同类型的黑素细胞肿瘤的BRAF和NRAS突变，并在一个子集中使用免疫组化观察MAPK通路活性。BRAF基因外显子15突变频率在常见获得性痣（CAN）中为14/16（87.5%），在CM中为9/12（75%），在Spitz痣中为0/26，在蓝色痣中为3/25（12%）（p <0.01）。我们研究了Spitz和蓝色痣是否表现出BRAF外显子II和/或NRAS外显子1和2突变的代偿性增加，以解释BRAF外显子15突变频率低。NRAS突变仅见于1/16例Spitz痣（6.3%）和0/15例蓝色痣。此外，在2/11例（18.2%）CAN和3/12例（25%）CM中发现NRAS突变。所有肿瘤均未显示BRAF外显子II突变。尽管它们的BRAF和NRAS突变频率较低，但Spitz痣表现出较强的MAPK通路激活，如通过双磷酸化ERK 1/2的细胞质表达所测量的，而蓝色痣具有较弱的通路激活。我们的结论是，BRAF和NRAS突变是不必要的黑素细胞肿瘤的发展，某些类型的肿瘤必须通过替代机制。(C)2004 Wiley-Liss，Inc.
Cutaneous melanoma (CM) is the most lethal form of skin cancer. Along with some benign melanocytic tumors, the majority shows BRAF or NRAS mutation, but it is not known whether these are essential to all forms of melanocytic neoplasia. We screened 79 melanocytic tumors of different types for BRAF and NRAS mutations and looked at MAPK pathway activity using immunohistochemistry in a subset. Significant differences in BRAF exon 15 mutation frequency were found: 14/16 (87.5%) in common acquired naevi (CANs), 9/12 (75%) in CMs, 0/26 in Spitz naevi and 3/25 (12%) in blue naevi (p < 0.01). We looked at whether Spitz and blue naevi showed a compensatory increase in BRAF exon II and/or NRAS exons 1 and 2 mutations to account for the low BRAF exon 15 mutation frequency. NRAS mutations were found in only 1/16 (6.3%) Spitz naevi and 0/15 blue naevi. In addition, NRAS mutations were found in 2/11 (18.2%) CANs and 3/12 (25%) CMs. None of the tumors showed BRAF exon II mutations. Despite their low combined BRAF and NRAS mutation frequency, Spitz naevi showed strong MAPK pathway activation as measured by cytoplasmic expression of dually phosphorylated ERK 1/2, while blue naevi had weak pathway activation. We conclude that BRAF and NRAS mutations are not necessary for melanocytic tumor development and that some types of tumor must arise by alternative mechanisms. (C) 2004 Wiley-Liss, Inc.