Intra- and Inter-Tumoral Homogeneity of BRAFV600E Mutations in Melanoma Tumors
Intra- and Inter-Tumoral Homogeneity of BRAFV600E Mutations in Melanoma Tumors
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DOI：
10.1038/jid.2015.229
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发表时间：
2015-12-01
影响因子：
6.5
通讯作者：
Rodriguez-Peralto, Jose L.
中科院分区：
文献类型：
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作者：
Riveiro-Falkenbach, Erica;Villanueva, Candida A.;Rodriguez-Peralto, Jose L.
靶向治疗时代为黑色素瘤患者带来了新的治疗视角。 BRAF(V600) 抑制剂治疗可改善携带 BRAF(V600) 突变的转移性黑色素瘤患者的总体生存率和无病生存率。尽管 BRAF(V600E) 突变似乎在肿瘤发生中起关键作用，但其在肿瘤进展过程中的表达仍存在争议。事实上，许多作者声称 BRAF(V600E) 异质性在黑色素瘤肿瘤中很明显。在此，我们研究了 140 名患者的匹配原发性和转移性样本中 BRAF(V600E) 的表达模式。通过结合实时 PCR 和免疫组织化学分析，我们证明了 BRAF(V600E) 表达在黑色素瘤肿瘤中是同质的，并假设其他人描述的异质性可能归因于使用分子方法时的技术问题。我们还证明了抗 BRAF(V600E) VE1 抗体可高效检测黑色素瘤中的 BRAF(V600E) 突变。
The era of targeted therapy has introduced a new therapeutic perspective for melanoma patients. Treatment with BRAF(V600) inhibitors has improved overall and disease-free survival in metastatic melanoma patients whose tumors harbor BRAF(V600) mutations. Although the BRAF(V600E) mutation appears to have a critical role in tumor initiation, its expression during tumor progression remains controversial. In fact, various authors claim that BRAF(V600E) heterogeneity is evident in melanoma tumors. Herein, we investigated the pattern of BRAF(V600E) expression in matched primary and metastatic samples from 140 patients. Using a combination of real-time PCR and immunohistochemical analyses, we demonstrated that BRAF(V600E) expression is homogeneous in melanoma tumors and hypothesized that the heterogeneity described by others might be attributable to technical issues when molecular methods are used. We also demonstrated the high efficiency of the anti-BRAF(V600E) VE1 antibody for the detection of BRAF(V600E) mutations in melanoma tumors.