JCO Precis Oncol:NF1突变与胃肠道肿瘤GIST发生有关

2017-08-19 佚名 medicalxpress

UC圣地亚哥摩尔斯癌症中心的研究人员已经确定,称为十二指肠 - 空肠弯曲或DJF的小肠特定区域显示出具有NF1基因突变的肿瘤(GIST)的高频率的胃肠道基质。研究结果发表在8月在线JIC精神肿瘤学杂志上。

UC圣地亚哥摩尔斯癌症中心的研究人员已经确定,称为十二指肠 - 空肠弯曲或DJF的小肠特定区域显示出具有NF1基因突变的肿瘤(GIST)的高频率的胃肠道基质。研究结果发表在8月在线JIC精神肿瘤学杂志上。


大约有30%的GIST发生的小肠分为三个解剖学,组织学和功能上不同的部分:十二指肠,空肠和回肠。大多数小肠GIST与KIT突变有关。然而,GIST的一个子集在其他基因如NF1中具有突变。

摩尔斯癌症中心外科肿瘤学家Jason Sicklick说:“十二指肠转变为空肠时,我们发现NF1突变的GIST过度表达。

NF1可以在体内(肿瘤DNA)或种系(被称为神经纤维瘤病1型[NF-1]的遗传病的一部分)中突变。患有NF-1突变的患者比未受影响的个体发生GIST的可能性高34倍。

Sicklick说:“这些病人中的一些患者的基因组检测显示隐匿性种系NF1突变,没有其他明显的NF-1临床症状。 “任何有GIST的人都应进行肿瘤基因检测,目前只有8%?15%的患者接受了检测,对于NF1突变患者,对遗传性NF-1阳性的患者的家庭成员有影响,因为他们也可能患上癌症的风险增加,包括GIST。”

根据美国国立卫生研究院的统计,NF-1是一种特征,其特征在于皮肤着色和沿着皮肤,脑部和身体其他部位(如胃肠道)的神经的肿瘤生长。这种情况的体征和症状在受影响人群中差别很大。 NF-1发生在全球3000到4000人中。

GIST代表胃肠道中最常见的肉瘤类型,美国的年发病率为每百万人6.8例。这些肿瘤从胃肠道壁的特殊细胞开始,称为Cajal(ICCs)的间质细胞。 ICC有时被称为胃肠道的“起搏器”,因为它们表明消化系统中的肌肉通过蠕动收缩,通过系统移动食物和液体。

莫氏癌中心的Sicklick和同事正在寻求一种逐渐抵抗治疗的GIST肿瘤的个性化方法。最终,有95%以上耐药GIST的患者屈服于癌症,强调了其他治疗靶点的必要性。

Moores癌症中心的医学肿瘤学家博士说:“GIST的患者应该用下一代测序板分析肿瘤。” “我们发现了一些患者的子集,包括KIT突变的患者,他们有下游突变可能会使他们对传统靶向治疗不敏感。”

Sicklick补充说:“这种洞察帮助医生知道哪些药物将会或将不会起作用,以便妥善治疗这些致命的肿瘤。在NF1突变体GIST中至关重要的是,标准的药物治疗方案是无效的。

Sicklick最近的GIST研究还发现了与GIST患者亚群相关的新基因融合和突变。他和他的团队也提供了第一个证据表明,Hedgehog信号通路是形成GIST的核心,它们经常由KIT致癌基因驱动。
原始出处:
Adam M. Burgoyne,Martina De Siena, Maha Alkhuziem.et al, Duodenal-Jejunal Flexure GI Stromal Tumor Frequently Heralds Somatic NF1 and Notch Pathway Mutations, JCO Precision Oncology

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    2017-10-21 lidong40
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    2017-11-26 ay2000fy
  4. 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GetPortalCommentsPageByObjectIdResponse(id=235089, encodeId=4d74235089c7, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo5nmIH5IQqCKjJgSCuicPWUWOUcdqt1ROPnEiaOYN4pSHibDv8la3OxNLalvuvUXn8clpJlrpuyTpckgt9OPkeSSdT/0, createdBy=8fd71930726, createdName=半夏微凉, createdTime=Sat Aug 19 12:01:11 CST 2017, time=2017-08-19, status=1, ipAttribution=)]
    2017-09-15 minlingfeng
  5. 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  6. 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  7. 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  8. 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href='/topic/show?id=bebe8032fc' target=_blank style='color:#2F92EE;'>#GIST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8032, encryptionId=bebe8032fc, topicName=GIST)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e445632366, createdName=july_977, createdTime=Mon Aug 21 02:41:00 CST 2017, time=2017-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235107, encodeId=f48623510e0e, content=学习了,好文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sat Aug 19 13:24:42 CST 2017, time=2017-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=235089, encodeId=4d74235089c7, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo5nmIH5IQqCKjJgSCuicPWUWOUcdqt1ROPnEiaOYN4pSHibDv8la3OxNLalvuvUXn8clpJlrpuyTpckgt9OPkeSSdT/0, createdBy=8fd71930726, createdName=半夏微凉, createdTime=Sat Aug 19 12:01:11 CST 2017, time=2017-08-19, status=1, ipAttribution=)]
    2017-08-21 july_977
  9. 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    2017-08-19 1ddf0692m34(暂无匿称)

    学习了,好文章

    0

  10. 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    2017-08-19 半夏微凉

    学习了谢谢分享

    0

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科学家们之前曾发现1型神经纤维瘤(NF1)基因与酒精依赖性有关,这种作用可能是通过调节γ-氨基丁酸(γ-GABA)来实现对酒精摄入的影响。最近的一篇文章,来自Scripps研究所的研究人员则发现γ-氨基丁酸这种神经递质能降低焦虑情绪,促进情绪的放松,研究人员指出这一发现将人体Nf1基因的突变,与酒精依赖性风险及严重程度联系在了一起。 这一研究成果公布在8月18日 Biologi