BRAF and NRAS mutations are frequent in nodular melanoma but are not associated with tumor cell proliferation or patient survival
BRAF and NRAS mutations are frequent in nodular melanoma but are not associated with tumor cell proliferation or patient survival
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DOI：
10.1111/j.0022-202x.2005.23788.x
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发表时间：
2005-08-01
影响因子：
6.5
通讯作者：
Kumar, R
中科院分区：
文献类型：
--
作者：
Akslen, LA;Angelini, S;Kumar, R
先前的研究表明，皮肤黑色素瘤中的BRAF（V-raf鼠肉瘤病毒癌基因同源物B1）或NRAS（神经母细胞瘤RAS病毒[V-ras]癌基因同源物）基因频繁突变，但这些改变与肿瘤细胞增殖之间的关系尚未在人类黑色素瘤中得到检验。在我们对 51 个原发性结节性黑色素瘤和 18 个配对转移瘤的研究中，我们在 15 个原发性肿瘤 (29%) 和 8 个转移瘤 (44%) 中发现 BRAF（密码子 600，之前表示为 599）突变。 NRAS 突变的数字分别为 27% 和 22%。除一例外，BRAF 和 NRAS 基因的突变在所有病例中都是相互排斥的，并且从原发肿瘤到转移瘤均保持不变。然而，突变与 Ki-67 表达、肿瘤厚度、微血管密度或血管侵袭的肿瘤细胞增殖无关，并且患者生存率也没有差异。尽管 BRAF 和 NRAS 突变可能对某些黑色素瘤的发生和维持很重要，但其他因素可能对侵袭性黑色素瘤亚组的增殖和预后更为重要。
Previous studies have shown frequent mutations in the BRAF (V-raf murine sarcoma viral oncogene homolog B1) or NRAS ( neuroblastoma RAS viral [V-ras] oncogene homolog) genes in cutaneous melanoma, but the relationship between these alterations and tumor cell proliferation has not been examined in human melanoma. In our study of 51 primary nodular melanomas and 18 paired metastases, we found mutations in BRAF ( codon 600, previously denoted 599) in 15 primary tumors (29%) and eight metastases (44%). The figures for NRAS mutations were 27% and 22%, respectively. Mutations in BRAF and NRAS genes were mutually exclusive in all but one case, and were maintained from primary tumors through their metastases. Mutations, however, were not associated with tumor cell proliferation by Ki-67 expression, tumor thickness, microvessel density, or vascular invasion, and there were no differences in patient survival. Although BRAF and NRAS mutations are likely to be important for the initiation and maintenance of some melanomas, other factors might be more significant for proliferation and prognosis in subgroups of aggressive melanoma.