Frequencies of NRAS and BRAF mutations increase from the radial to the vertical growth phase in cutaneous melanoma.
Frequencies of NRAS and BRAF mutations increase from the radial to the vertical growth phase in cutaneous melanoma.
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DOI：
10.1038/jid.2008.374
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发表时间：
2009-06
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影响因子：
--
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中科院分区：
文献类型：
--
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关于个体黑色素瘤肿瘤径向（RGP）和垂直（VGP）生长期NRAS和BRAF突变的相对发生率缺乏共识。本研究旨在检验突变是随着从RGP进展为VGP而获得的假设。使用激光捕获显微切割，从15个原位黑色素瘤和29个侵袭性肿瘤的RGP和VGP中获得纯肿瘤DNA。PCR扩增NRAS外显子2和BRAF外显子15 DNA并测序。15例原位黑色素瘤中有6例（40%）存在突变。29例浸润性肿瘤中有16例显示RGP突变（55.2%），22例显示VGP突变（75.9%）。配对RGP/VGP突变分析显示突变分布有不一致的趋势，有利于VGP定位（p = 0.07）。12/15例在两个阶段都有突变的样本在VGP中的突变DNA比例增加，在DNA色谱图上测量（p = 0.08）。本研究的局限性包括由于技术原因从较大人群中选择的样本队列相对较小，存在选择偏倚的风险。尽管存在这些问题，但我们的研究结果支持了NRAS和BRAF突变随着肿瘤从浅表性疾病进展为浸润性疾病而增加的假设。
A lack of consensus exists regarding the relative rates of NRAS and BRAF mutations in the radial (RGP) and vertical (VGP) growth phases of individual melanoma tumors. This study was conducted to test the hypothesis that mutations are acquired with progression from RGP to VGP. Using laser capture microdissection, pure tumor DNA was obtained from fifteen in-situ melanomas, and from the RGP and VGP of twenty-nine invasive tumors. NRAS exon 2 and BRAF exon 15 DNA were amplified by PCR and sequenced. Mutations were present in six of fifteen in-situ melanomas (40%). Sixteen of twenty-nine invasive tumors exhibited RGP mutations (55.2%); 22 showed VGP mutations (75.9%). Paired RGP/VGP mutation analysis revealed a trend toward discordance in the distribution of mutations, favoring VGP localization (p = 0.07). Twelve of fifteen samples with mutations in both phases had an increased proportion of mutated DNA in the VGP, measured on DNA chromatograms (p = 0.08). Limitations of this study include a relatively small sample cohort selected for technical reasons from a larger population, presenting the risk of selection bias. These concerns notwithstanding, our findings support the hypothesis that NRAS and BRAF mutations increase with tumor progression from superficial to invasive disease.
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