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首页> 外文学位 >NRAS and BRAF mutations in primary cutaneous melanoma: A comparison of mutation rates between radial and vertical growth phases in individual tumors.
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NRAS and BRAF mutations in primary cutaneous melanoma: A comparison of mutation rates between radial and vertical growth phases in individual tumors.

机译：原发性皮肤黑素瘤中的NRAS和BRAF突变：单个肿瘤在径向和垂直生长期之间的突变率比较。

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摘要

Primary cutaneous melanoma is a cancer arising from melanocytes in the skin. In recent decades the incidence of this malignancy has increased significantly. Mortality rates are high for patients with tumors measuring over a few millimeters in thickness. Response rates to conventional radiation and chemotherapy are very low in patients with metastatic melanoma. New therapies targeting melanoma's aberrant cell signaling pathways such as the MAP Kinase pathway are being developed. Mutations of NRAS and BRAF genes are quite common in cutaneous melanoma and lead to constitutive activation of the MAP Kinase pathway. This study tests the hypothesis that NRAS and BRAF mutations increase as a tumor progresses from the noninvasive radial growth phase (RGP) to the invasive vertical growth phase (VGP). Laser capture microdissection was used to obtain separate, pure tumor DNA samples from the RGP and VGP of thirty primary cutaneous melanomas. PCR was used to amplify NRAS exon 2 and BRAF exon 15 tumor DNA. The amplified DNA was sequenced and analyzed for mutations. An overall mutation rate of 74% was obtained for the twenty-three melanomas in which there were complete sequence results. With the exception of one melanoma NRAS and BRAF mutations were mutually exclusive. All seven NRAS exon 2 mutations involved codon 61. Three of these melanomas had mutations in both the RGP and VGP. The remaining four tumors were wild type for NRAS exon 2 in the RGP but mutated in the VGP. Of the fifteen BRAF exon 15 mutated melanomas all but one involved codon 600. Twelve of the fifteen BRAF exon 15 mutations were the T1799A type. Nine of the fifteen BRAF mutated tumors had the same mutation in both the RGP and VGP. Five of fifteen melanomas had wild type RGP DNA and BRAF exon 15 mutated VGP DNA. A single melanoma had BRAF exon 15 mutated DNA in the RGP and wild type DNA in the VGP. Overall, these results suggest a trend toward the acquisition of NRAS and BRAF mutations as cutaneous melanomas change from a noninvasive to an invasive, potentially deadly cancer.
机译：原发性皮肤黑色素瘤是由皮肤中黑色素细胞引起的癌症。在最近的几十年中，这种恶性肿瘤的发病率显着增加。对于厚度超过几毫米的肿瘤患者，死亡率很高。转移性黑色素瘤患者对常规放疗和化疗的反应率非常低。正在开发针对黑色素瘤的异常细胞信号传导途径（如MAP激酶途径）的新疗法。 NRAS和BRAF基因的突变在皮肤黑色素瘤中非常普遍，并导致MAP激酶途径的组成性激活。这项研究检验了NRAS和BRAF突变随着肿瘤从无创放射状生长期（RGP）进入有创垂直生长期（VGP）而增加的假说。激光捕获显微切割用于从三十个原发性皮肤黑素瘤的RGP和VGP中获得单独的纯净肿瘤DNA样本。 PCR被用于扩增NRAS外显子2和BRAF外显子15肿瘤DNA。对扩增的DNA进行测序并分析突变。对于具有完整序列结果的二十三个黑色素瘤，总突变率为74％。除了一种黑色素瘤，NRAS和BRAF突变是互斥的。所有七个NRAS外显子2突变都涉及第61位密码子。这些黑素瘤中的三个在RGP和VGP中都有突变。其余的四个肿瘤是RGP中NRAS外显子2的野生型，但在VGP中突变。在15个BRAF外显子的15个突变的黑色素瘤中，除1个外，其他都涉及密码子600。15个BRAF外显子15的突变中的12个是T1799A型。 15种BRAF突变的肿瘤中有9种在RGP和VGP中具有相同的突变。 15个黑色素瘤中有5个具有野生型RGP DNA和BRAF外显子15突变的VGP DNA。单个黑色素瘤在RGP中具有BRAF外显子15突变的DNA，在VGP中具有野生型DNA。总体而言，这些结果表明，随着皮肤黑色素瘤从非侵袭性变为侵袭性，可能致命的癌症，获得NRAS和BRAF突变的趋势。

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  • 作者

    Greene, Victoria R.;

  • 作者单位

    The University of Texas School of Public Health.$bEpidemiology & Disease Control.;

  • 授予单位 The University of Texas School of Public Health.$bEpidemiology & Disease Control.;
  • 学科 Biology Genetics.; Health Sciences Public Health.; Health Sciences Oncology.
  • 学位 M.P.H.
  • 年度 2007
  • 页码 46 p.
  • 总页数 46
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 遗传学;预防医学、卫生学;肿瘤学;
  • 关键词

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