JCO Precis Oncol:原发性和转移性前列腺肿瘤的前瞻性综合基因组分析

2019-07-06 AlexYang MedSci原创

综合基因组分析(CGP)在常规前列腺癌临床治疗中越来越多的被使用。最近,有研究人员为了指定有针对性的治疗策略,利用CGP对3476例临床晚期前列腺肿瘤进行了基因组变异(GAs)和基因组不稳定特性分析。前列腺癌样本包括了1660个原发性位点和1816个转移性肿瘤位点。研究人员对这些样本进行了CGP前瞻性分析。研究发现,高频变异基因包括TP53 (44%)、PTEN (32%)、TMPRSS2-ERG

综合基因组分析(CGP)在常规前列腺癌临床治疗中越来越多的被使用。最近,有研究人员为了指定有针对性的治疗策略,利用CGP对3476例临床晚期前列腺肿瘤进行了基因组变异(GAs)和基因组不稳定特性分析。
 
前列腺癌样本包括了1660个原发性位点和1816个转移性肿瘤位点。研究人员对这些样本进行了CGP前瞻性分析。研究发现,高频变异基因包括TP53 (44%)、PTEN (32%)、TMPRSS2-ERG (31%)和AR (23%)。潜在靶向Gas通常存在于DNA修复途径、磷脂酰肌醇3激酶和RAS/RAF/MEK途径。DNA修复途径的GAs包括同源重组修复(23%)、凡科尼贫血(5%)、CDK12(6%)和错配修复(4%)。BRCA1/2、ATR和FANCA GAs与高gLOH相关,而CDK12变异肿瘤则很少表现出高gLOH。另外,TMB均值低(2.6变异/Mb)。更多的是,一小部分案例(3%)具有高TMB,且其中71%的案例同时具有高MSI。与原发性肿瘤相比,转移位点肿瘤在11q13扩增子中富集(CCND1/FGF19/FGF4/FGF3),GAs在AR, LYN, MYC, NCOR1, PIK3CB和RB1中富集。
 
最后,研究人员指出,常规临床CGP鉴定的GAs是57%案例中针对性治疗的可调查生物标记。gLOH和MSI/TMB特性分别能够进一步的促进多聚酶抑制剂和免疫治疗的选择。结合gLOH与DNA修复GAs的相关性鉴定除了与同源重组缺陷相关的基因。GAs富集在转移位点肿瘤中表明了转移性前列腺癌的治疗策略。临床结果相关性的缺乏是他们研究的一个限制因素。
 
原始出处:
 
Chung JH, Dewal N, Sokol E et al. Prospective Comprehensive Genomic Profiling of Primary and Metastatic Prostate Tumors. JCO Precis Oncol. 2019
 
本文系梅斯医学(MedSci)原创编译整理,转载需授权!
 

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    2020-06-04 智智灵药
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    2019-08-16 minlingfeng
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    2019-07-06 anti-cancer

    谢谢梅斯分享这么多精彩信息

    0

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强生创新(Johnson & Johnson Innovation)日前宣布,其科研人员在《Nature Communications》上发表了一篇最新论文,揭露了免疫系统在肺癌早期发展中的作用。这一研究是大型科研项目“癌前基因组图谱”(Pre-Cancer Genome Atlas,缩写PGCA)中的一环。总体来看,这个项目想要找到参与癌症早期发展的潜在因素,从而帮助人们在尽早的阶段进行检测和干

Allergy:青少年中关于DNA甲基化和过敏性敏感的基因组纵向研究

过敏性敏感的存在对儿童常见的哮喘和鼻炎的发展具有重要的影响。过敏性敏感的病因仍旧不清楚,并且其潜在的机制还没有建立。一些研究表明一些CpGs的DNA甲基化(DNAm)与过敏性敏感相关。然而,尚没有研究关注青少年时期。最近,有研究人员使用线性混合模型评估了青春期前后全基因组DNAm与室内、室外和食物过敏原过敏敏感之间相关性。研究发现,通过线性混合模型,鉴定了35个CpGs与过敏性敏感相关(错误发现率