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CLIN CANCER RES:克罗恩病相关结直肠肿瘤发生的基因改变情况

2018-10-29 MedSci MedSci原创

炎症性肠病患者(溃疡性结肠炎和克罗恩病(CD))患结直肠癌(CRC)的风险增加。溃疡性结肠炎研究的证据表明,TP53突变代表了从炎症结肠上皮向CRC发展的第一步。然而,CD患者向CRC的演变机制尚不清楚。CLIN CANCER RES近期发表了一篇文章研究这一问题。

炎症性肠病患者(溃疡性结肠炎克罗恩病(CD))患直肠癌(CRC)的风险增加。溃疡性结肠炎研究的证据表明,TP53突变代表了从炎症结肠上皮向CRC发展的第一步。然而,CD患者向CRC的演变机制尚不清楚。CLIN CANCER RES近期发表了一篇文章研究这一问题。

作者对563个癌症相关基因进行靶向二代测序,分析了来自28个CD-CRC患者的73个组织标本。将结果与具有相似组织形态学的24个散发性CRC(即粘液腺癌)以及TCGA中的数据进行比较。研究结果表明,CD-CRC体细胞拷贝数改变(SCNAs)与散发性CRC相似。但有一个值得注意的例外:CD-CRC中5p显着增加更为普遍。CD-CRC具有明显的突变特征:TP53(CD-CRC中76%,散发性粘液性CRC中33%),KRAS(24%vs 50%),APC(17%vs 75%)和SMAD3( 3%vs 29%)。TP53突变和SCNAs是CD进展中的早期频繁出现的事件。而APC,KRAS和SMAD2 / 4突变发生较晚。在4名患有CD-CRC的患者中,至少一种突变和/或SCNA存在于未发育异常的结肠粘膜中,表明隐匿性的肿瘤进展。

文章最后认为,CD-CRC和癌变前的分子谱分析揭示了炎症相关的基因组改变情况:肿瘤发展早期出现5p增加和TP53突变。检测癌前病变中的这些异常基因可能有助于预测疾病进展并区分CD相关和散发性结直肠肿瘤。

原始出处:

Daniela Hirsch, Darawalee Wangsa, et al. Dynamics of Genome Alterations in Crohn's Disease–Associated Colorectal Carcinogenesis. CLIN CANCER RES. October 2018 doi: 10.1158/1078-0432.CCR-18-0630

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    2018-10-30 kafei

    学习了谢谢

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