Conserved recurrent gene mutations correlate with pathway deregulation and clinical outcomes of lung adenocarcinoma in never-smokers.
Conserved recurrent gene mutations correlate with pathway deregulation and clinical outcomes of lung adenocarcinoma in never-smokers.
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DOI：
10.1186/1755-8794-7-32
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发表时间：
2014-06-04
影响因子：
2.7
通讯作者：
Yang P
中科院分区：
文献类型：
--
作者：
Sun Z;Wang L;Eckloff BW;Deng B;Wang Y;Wampfler JA;Jang J;Wieben ED;Jen J;You M;Yang P
需要新的和可靶向的突变来提高对不吸烟者肺癌的认识和治疗。用外显子组和mRNA-seq对27例不吸烟者肺腺癌进行测序。检测体细胞突变，并将其与通路失调、肿瘤表型和临床结果进行比较。尽管每个肿瘤中DNA或mRNA的体细胞突变从数百到数千不等，但两者之间的重叠突变只有几到几百个。来自DNA或mRNA的体细胞突变数量与临床变量无显著相关；然而，重叠突变的数量与癌症亚型相关。这些重叠突变优先在mRNA中表达，mRNA中的等位基因频率始终高于DNA。10个基因（EGFR、TP53、KRAS、RPS6KB2、ATXN2、DHX9、PTPN13、SP1、SPTAN1和MYOF）发生复发性突变，这些突变与通路失调和患者生存高度相关。存在于DNA和RNA中的复发性突变可能是肿瘤生物学、通路解除管制和临床结果的驱动因素。这些信息可用于患者分层和治疗靶点的开发。
Novel and targetable mutations are needed for improved understanding and treatment of lung cancer in never-smokers. Twenty-seven lung adenocarcinomas from never-smokers were sequenced by both exome and mRNA-seq with respective normal tissues. Somatic mutations were detected and compared with pathway deregulation, tumor phenotypes and clinical outcomes. Although somatic mutations in DNA or mRNA ranged from hundreds to thousands in each tumor, the overlap mutations between the two were only a few to a couple of hundreds. The number of somatic mutations from either DNA or mRNA was not significantly associated with clinical variables; however, the number of overlap mutations was associated with cancer subtype. These overlap mutants were preferentially expressed in mRNA with consistently higher allele frequency in mRNA than in DNA. Ten genes (EGFR, TP53, KRAS, RPS6KB2, ATXN2, DHX9, PTPN13, SP1, SPTAN1 and MYOF) had recurrent mutations and these mutations were highly correlated with pathway deregulation and patient survival. The recurrent mutations present in both DNA and RNA are likely the driver for tumor biology, pathway deregulation and clinical outcomes. The information may be used for patient stratification and therapeutic target development.
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DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
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DOI：
10.1158/1078-0432.ccr-11-2511
发表时间：
2012-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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作者：
Zhang Y;Sun Y;Pan Y;Li C;Shen L;Li Y;Luo X;Ye T;Wang R;Hu H;Li H;Wang L;Pao W;Chen H
通讯作者：
Chen H
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
DOI：
10.1093/bioinformatics/btr612
发表时间：
2012-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Asmann YW;Middha S;Hossain A;Baheti S;Li Y;Chai HS;Sun Z;Duffy PH;Hadad AA;Nair A;Liu X;Zhang Y;Klee EW;Kalari KR;Kocher JP
通讯作者：
Kocher JP
影响因子：
56.9
作者：
Wang, ZH;Shen, D;Velculescu, VE
通讯作者：
Velculescu, VE