Br J Dermatol:后天性黑素细胞痣的BRAF和NRAS突变提示MAPK信号通路的激活

2017-07-24 xiaoxiao MedSci原创

痣有广义和狭义之分,广义包括各种先天性、后天性黑素细胞痣、皮脂腺痣等。医学的“痣”是狭义的,又称痣细胞痣、色素痣、黑素细胞痣或普通获得性黑色素细胞痣,不包括先天性黑色素细胞痣。痣为人类最常见的良性皮肤肿瘤,是表皮、真皮内黑素细胞增多引起的皮肤表现。根据痣细胞在皮肤内的位置不同,可将其分为交界痣、混合痣和皮内痣。扁平皮损提示为交界痣,略高起皮损多为混合痣,而乳头瘤样皮损和几乎所有半球状和带蒂皮损为皮

痣有广义和狭义之分,广义包括各种先天性、后天性黑素细胞痣、皮脂腺痣等。医学的“痣”是狭义的,又称痣细胞痣、色素痣、黑素细胞痣或普通获得性黑色素细胞痣,不包括先天性黑色素细胞痣。痣为人类最常见的良性皮肤肿瘤,是表皮、真皮内黑素细胞增多引起的皮肤表现。根据痣细胞在皮肤内的位置不同,可将其分为交界痣、混合痣和皮内痣。扁平皮损提示为交界痣,略高起皮损多为混合痣,而乳头瘤样皮损和几乎所有半球状和带蒂皮损为皮内痣。

后天性黑素细胞痣可以有独特的皮肤镜模式,对应于不同的解剖学的生长模式。前人关于后天痣皮肤镜图像分层的研究的内容,主要集中在体细胞BRAF基因的突变频率,而NRAS突变仍有待进一步研究。来自意大利的研究人员在后天痣的不同皮肤镜亚型中探讨了BRAF突变和NRAS突变的发生率及MAPK信号通路的激活情况。主要内容如下:

研究方法:在1261例符合条件的参与者中挑选出了27例(男性19例,女性8例;平均年龄46.7岁)有后天痣的患者,他们共有40个后天痣分别为球状痣、网状痣和球周缘痣(PG痣),研究人员评估了这些后天痣中是否存在BRAF突变和NRAS突变。使用高灵敏度和高分辨的QX200微滴式数字PCR (ddPCR) 系统来确定突变。

研究人员在85%的后天痣 (n=34/40)中检测到了BRAFV600E(c.1799T>A or c.1799_1800delTGinsA)突变和BRAFV600K突变。所有野生型BRAF痣(15%;n=6/40)携带有有NRAS密码子12/13或61突变。BRAF基因突变发生率如下:在球状痣中为92%(n=12/13);在PG痣中为100%(n = 12/12);而在网状痣中:分别为67%(n = 10/15)出现BRAF突变和33%(n = 5/15)出现NRAS突变(P = 0.037)。

总之,本研究评估的后天性痣100%存在BRAF或NRAS突变。采用单细胞突变的敏感检测技术发现,所有的后天性痣最终都会发生BRAF和NRAS突变。由于这些突变在不同的皮肤镜痔亚群中普遍存在,本研究赞同MAPK信号通路作用于良性黑素细胞的进展,这表明除了体细胞突变,额外的BRAF和NRAS突变是黑色素瘤进展的必须条件。

原始出处:

Tan JM, Tom LN,et al.The BRAF and NRAS mutation prevalence in dermoscopic subtypes of acquired naevi reveals constitutive MAPK pathway activation.Br J Dermatol. 2017 Jul 17. doi: 10.1111/bjd.15809. [Epub ahead of print]

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    2017-10-25 lidong51
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    2018-04-25 tcm99hq
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    2017-07-26 laoli

    学习了,谢谢分享!

    0

  5. 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    2017-07-26 zhaojie88
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    2017-07-26 yese
  7. 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createdBy=74c2229, createdName=tcm99hq, createdTime=Wed Apr 25 23:28:00 CST 2018, time=2018-04-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1947604, encodeId=06b2194e604fe, content=<a href='/topic/show?id=1d2513030c6' target=_blank style='color:#2F92EE;'>#NRAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13030, encryptionId=1d2513030c6, topicName=NRAS突变)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/PiajxSqBRaEKxsKDoOOFxGpMibw6lsQFUIicWt7kWGevkdgFhjiban1icD2JdIBmjVo7qX7aSlCSpiaia382nuLKiaI3Cg/132, createdBy=5c442500150, createdName=ms9474365431325850, createdTime=Sat Mar 24 11:28:00 CST 2018, time=2018-03-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=226628, encodeId=a22e22662887, content=学习了,谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLC1BMzZWdMSPQWuib6BtQGicK8ygGBM6YakpfkRc67soFSuKbZr86enL1KggQZEZbgWSeicJibafmYfQ3AibicIHMwwicmDShfRFvvI38/0, createdBy=272a110164, createdName=laoli, createdTime=Wed Jul 26 19:39:40 CST 2017, time=2017-07-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1354967, encodeId=d685135496e47, content=<a href='/topic/show?id=6de63659ed' target=_blank style='color:#2F92EE;'>#BRAF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3659, encryptionId=6de63659ed, topicName=BRAF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Wed Jul 26 09:28:00 CST 2017, time=2017-07-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1487625, 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  8. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLC1BMzZWdMSPQWuib6BtQGicK8ygGBM6YakpfkRc67soFSuKbZr86enL1KggQZEZbgWSeicJibafmYfQ3AibicIHMwwicmDShfRFvvI38/0, createdBy=272a110164, createdName=laoli, createdTime=Wed Jul 26 19:39:40 CST 2017, time=2017-07-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1354967, encodeId=d685135496e47, content=<a href='/topic/show?id=6de63659ed' target=_blank style='color:#2F92EE;'>#BRAF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3659, encryptionId=6de63659ed, topicName=BRAF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Wed Jul 26 09:28:00 CST 2017, time=2017-07-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1487625, 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time=2017-07-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585297, encodeId=f998158529ea5, content=<a href='/topic/show?id=792b15145a6' target=_blank style='color:#2F92EE;'>#RAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15145, encryptionId=792b15145a6, topicName=RAS突变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6f2c17156536, createdName=bioon7, createdTime=Wed Jul 26 09:28:00 CST 2017, time=2017-07-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=226060, encodeId=ccbc226060b7, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, 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    2017-07-26 bioon7
  9. 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    2017-07-25 189****7206

    学习了谢谢分享

    0

  10. 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    2017-07-24 林3301

    不错,了解分享一下

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