Analysis of the B-RafV600E mutation in cutaneous melanoma patients with occupational sun exposure.

Analysis of the B-RafV600E mutation in cutaneous melanoma patients with occupational sun exposure.
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DOI:
10.3892/or.2014.2977
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发表时间:
2014-03
期刊:
影响因子:
4.2
通讯作者:
Libra M
Libra M
中科院分区:
医学3区
文献类型:
--
作者:
Candido S;Rapisarda V;Marconi A;Malaponte G;Bevelacqua V;Gangemi P;Scalisi A;McCubrey JA;Maestro R;Spandidos DA;Fenga C;Libra M

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阳光照射是皮肤肿瘤发生的危险因素之一。在黑色素瘤中,Ras-Raf-MEK-ERK(MAPK)信号通路通过多种机制(包括B-RAF突变)被组成性激活。据推测,黑素细胞病变中的B-RAF突变是由紫外线(UV)辐射诱导的DNA损伤引起的。然而,它仍然是讨论,如果B-RAF突变与黑色素瘤患者暴露于阳光。因此,在本研究中,已知的B-RAFV600E突变进行了分析,从30个室内和38个室外工作者的黑色素瘤样本。室外作业者和室内作业者B-RAFV600E突变检出率分别为52%和73%。值得注意的是,在室内工作者中诊断的14例躯干黑色素瘤中有12例(85%),在室外工作者中诊断的19例样本中有9例(47%)(p = 0.03)。通过分析其他身体部位的黑色素瘤,在工人组之间没有发现B-RAFV600E突变频率的统计学差异。在室内工作者中检测到的突变似乎与娱乐性或间歇性暴露于阳光有关,因为通常躯干是一个受阳光保护的身体部位。总的来说,这些数据表明在黑色素瘤中检测到的B-RAFV600E突变与长期暴露于阳光下无关。在其他基因中检测到的突变也可能导致暴露于紫外线辐射的患者亚组中黑色素瘤的发展。
Sun-exposure is one of the risk factors associated with the development of a cutaneous neoplasm. In melanoma, the Ras-Raf-MEK-ERK (MAPK) signaling pathway is constitutively activated through multiple mechanisms, including B-RAF mutation. It has been hypothesized that B-RAF mutations in melanocytic lesions arise from DNA damage induced by ultraviolet (UV) radiation. However, it is still discussed if B-RAF mutations are associated with melanoma patients exposed to the sun. Therefore, in the present study, the known B-RAFV600E mutation was analysed in melanoma samples from 30 indoor and 38 outdoor workers. B-RAFV600E mutation was detected in 52 and 73% of outdoor workers and indoor workers, respectively. Of note, this mutation was identified in 12 of 14 (85%) melanoma of the trunk diagnosed in indoor workers and in 9 of 19 (47%) samples from outdoor workers (p=0.03). By analyzing melanomas of other body sites, no statistical difference in the frequency of B-RAFV600E mutation was identified between the groups of workers. It appears that the mutation detected among indoor workers may be associated with a recreational or intermittent exposure to the sun, as usually the trunk is a sun-protected body site. Overall, these data indicate that the B-RAFV600E mutation detected in melanoma is not associated with a chronic exposure to the sun. Mutations detected in other genes may also contribute to melanoma development in the subset of patients exposed to UV radiation.
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发表时间: 2014-06-01
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