Integrated Oncogenomic Profiling of Copy Numbers and Gene Expression in Lung Adenocarcinomas without EGFR Mutations or ALK Fusion.
Integrated Oncogenomic Profiling of Copy Numbers and Gene Expression in Lung Adenocarcinomas without EGFR Mutations or ALK Fusion.
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无 EGFR 突变或 ALK 融合的肺腺癌拷贝数和基因表达的综合肿瘤基因组分析
DOI：
10.7150/jca.23909
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发表时间：
2018
影响因子：
3.9
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Luo Y;Li B;Zhang G;He Y;Bae JH;Hu F;Cui R;Liu R;Wang Z;Wang L
基于EGFR突变或ALK融合癌基因的靶向治疗已成为某些肺腺癌（LUAD）患者的标准治疗方法。然而，大多数LUAD患者没有EGFR突变或ALK融合，其癌基因改变仍有待明确。在这里，我们对公共数据集进行了综合分析，以评估23个高度肺癌相关基因的基因组改变。在10例无EGFR突变或ALK融合的LUAD患者的微解剖、配对肿瘤和正常肺组织中测量这些基因的拷贝数。肿瘤组织中PTEN、RB1、HMGA2和PTPRD的拷贝数低于正常组织。尽管肿瘤中PTEN和RB1的mRNA水平降低，但拷贝数与表达之间仅存在PTEN的相关性。此外，对这23个基因拷贝数变化的分析揭示了EMSY/CCND1、EMSY/PIK3CA、CCND1/CDKN2A和CCND1/PIK3CA之间的相关性。我们对整合拷贝数和基因表达分析的探索优先考虑了PTEN-PIK3CA和RB1-CCND1通路，以制定无EGFR突变或ALK融合的LUAD患者的治疗策略。
Targeted therapies based on EGFR mutations or on the ALK fusion oncogene have become the standard treatment for certain patients with lung adenocarcinoma (LUAD). However, most LUAD patients have no EGFR mutation or ALK fusion, and their oncogenetic alterations remain to be characterized. Here we conducted an integrated analysis of public datasets to assess the genomic alterations of 23 highly lung cancer-associated genes. The copy numbers of these genes were measured in ten micro-dissected, paired tumors and normal lung tissues of LUAD patients without EGFR mutations or ALK fusion. The copy numbers of PTEN, RB1, HMGA2, and PTPRD were lower in tumors compared with those for normal tissues. Although there were reduced mRNA levels of PTEN and RB1 in tumors, there was a correlation between copy number and expression only for PTEN. In addition, analysis of the copy number alterations of these 23 genes revealed correlations between EMSY/CCND1, EMSY/PIK3CA, CCND1/CDKN2A, and CCND1/PIK3CA. Our exploration of integrated copy number and gene expression analysis gives priority to the PTEN-PIK3CA and RB1-CCND1 pathways in developing therapeutic strategies for LUAD patients without EGFR mutations or ALK fusion.
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影响因子：
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