Genomic and transcriptional alterations in lung adenocarcinoma in relation to EGFR and KRAS mutation status.
Genomic and transcriptional alterations in lung adenocarcinoma in relation to EGFR and KRAS mutation status.
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DOI：
10.1371/journal.pone.0078614
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Staaf J
中科院分区：
文献类型：
--
作者：
Planck M;Edlund K;Botling J;Micke P;Isaksson S;Staaf J
在肺腺癌中，突变谱以EGFR和KRAS突变为主。关于突变定义的亚组内和亚组之间的基因组和转录改变的知识的改进可以识别参与疾病发展或进展的基因。来自457个腺癌的基因组图谱，包括113个EGFR突变的、134个KRAS突变的和210个EGFR和KRAS野生型肿瘤（EGFRwt/KRASwt），以及来自914个腺癌的基因表达图谱，包括309个EGFR突变的、192个KRAS突变的和413个EGFRwt/KRASwt肿瘤，从不同的储存库中组装。通过监督和非监督方法分析了三个突变组之间的基因组和转录差异。 EGFR突变的腺癌显示了更大数量的拷贝数改变和复发扩增，总杂合性丢失的比例更高，更高的基因组复杂性，和更独特的表达模式比EGFR野生型腺癌。当三个突变组按阶段、性别和吸烟状况分层时，这些差异中的一些也是一致的。特异性拷贝数改变与突变状态相关，主要包括EGFR突变肿瘤中频率最高的增益区域。差异区域包括1 p、5 q34-q35.3、7 p、7q11.21、12p12.1、16 p和21 q上的大区域和小区域的增益，以及6q16.3-q21、8 p和9 p上的损失，突变组之间的频率差异为20-40%。有监督的基因表达分析确定了96个突变组之间一致的差异表达基因，与无监督的分析一起，这些分析突出了将三个突变组广泛解析为不同转录实体的困难。我们提供了一个全面的概述基因组和转录景观在肺腺癌分层EGFR和KRAS突变。我们的分析表明，肺腺癌的整体基因组和转录景观的影响，但只有在很小的程度上，EGFR和KRAS突变状态。
In lung adenocarcinoma, the mutational spectrum is dominated by EGFR and KRAS mutations. Improved knowledge about genomic and transcriptional alterations in and between mutation-defined subgroups may identify genes involved in disease development or progression. Genomic profiles from 457 adenocarcinomas, including 113 EGFR-mutated, 134 KRAS-mutated and 210 EGFR and KRAS-wild type tumors (EGFRwt/KRASwt), and gene expression profiles from 914 adenocarcinomas, including 309 EGFR-mutated, 192 KRAS-mutated, and 413 EGFRwt/KRASwt tumors, were assembled from different repositories. Genomic and transcriptional differences between the three mutational groups were analyzed by both supervised and unsupervised methods. EGFR-mutated adenocarcinomas displayed a larger number of copy number alterations and recurrent amplifications, a higher fraction of total loss-of-heterozygosity, higher genomic complexity, and a more distinct expression pattern than EGFR-wild type adenocarcinomas. Several of these differences were also consistent when the three mutational groups were stratified by stage, gender and smoking status. Specific copy number alterations were associated with mutation status, predominantly including regions of gain with the highest frequency in EGFR-mutated tumors. Differential regions included both large and small regions of gain on 1p, 5q34-q35.3, 7p, 7q11.21, 12p12.1, 16p, and 21q, and losses on 6q16.3-q21, 8p, and 9p, with 20-40% frequency differences between the mutational groups. Supervised gene expression analyses identified 96 consistently differentially expressed genes between the mutational groups, and together with unsupervised analyses these analyses highlighted the difficulty in broadly resolving the three mutational groups into distinct transcriptional entities. We provide a comprehensive overview of the genomic and transcriptional landscape in lung adenocarcinoma stratified by EGFR and KRAS mutations. Our analyses suggest that the overall genomic and transcriptional landscape of lung adenocarcinoma is affected, but only to a minor extent, by EGFR and KRAS mutation status.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
核苷酸分辨率上杂合性丧失和单相表达的全基因组丧失的综合分析揭示了三阴性乳腺癌的途径中断。
影响因子：
7
作者：
Ha G;Roth A;Lai D;Bashashati A;Ding J;Goya R;Giuliany R;Rosner J;Oloumi A;Shumansky K;Chin SF;Turashvili G;Hirst M;Caldas C;Marra MA;Aparicio S;Shah SP
通讯作者：
Shah SP
EGFR和KRAS突变的NSCLC之间的基因组广泛的SNP比较分析以及非小细胞肺癌中的两种致癌合作模型的表征。
影响因子：
2.7
作者：
Blons, Helene;Pallier, Karine;Le Corre, Delphine;Danel, Claire;Tremblay-Gravel, Maxime;Houdayer, Claude;Fabre-Guillevin, Elizabeth;Riquet, Marc;Dessen, Philippe;Laurent-Puig, Pierre
通讯作者：
Laurent-Puig, Pierre
影响因子：
64.8
作者：
通讯作者：
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影响因子：
3.8
作者：
Newnham GM;Conron M;McLachlan S;Dobrovic A;Do H;Li J;Opeskin K;Thompson N;Wright GM;Thomas DM
通讯作者：
Thomas DM