Whole genome exon arrays identify differential expression of alternatively spliced, cancer-related genes in lung cancer.
Whole genome exon arrays identify differential expression of alternatively spliced, cancer-related genes in lung cancer.
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DOI：
10.1093/nar/gkn697
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发表时间：
2008-11
影响因子：
14.9
通讯作者：
Godfrey TE
中科院分区：
文献类型：
--
作者：
Xi L;Feber A;Gupta V;Wu M;Bergemann AD;Landreneau RJ;Litle VR;Pennathur A;Luketich JD;Godfrey TE
mRNA 前体转录物的替代加工是真核生物蛋白质多样性的主要来源，并且与包括癌症在内的多种疾病过程有关。在这项研究中，我们对肺腺癌中的选择性剪接事件进行了全基因组分析。我们发现 17,800 个核心 Refseq 基因中的 2369 个似乎具有替代转录物，这些转录物在肺腺癌中与正常人中存在差异表达。根据已知的功能，这些基因的最大子集 (30.8%) 被认为与癌症相关。使用 PCR、定量 RT-PCR 和 DNA 测序对多个基因进行详细分析。我们发现肺肿瘤中 ERG 变体 2 过表达，但变体 1 没有过表达；肺肿瘤中 CEACAM1 变体 1 过表达，但变体 2 没有过表达，但在乳腺或结肠肿瘤中没有过表达。我们还鉴定了 CDH3 的新的过度表达变体，并验证了从 CDKN2A 基因座转录的 P16 的新变体的存在和过度表达。这些发现证明了对替代前 mRNA 加工的分析如何能够进一步阐明肿瘤和正常组织之间以及不同肿瘤类型之间的差异。此类研究可能会导致肿瘤诊断、预后和治疗的其他工具的开发。
Alternative processing of pre-mRNA transcripts is a major source of protein diversity in eukaryotes and has been implicated in several disease processes including cancer. In this study we have performed a genome wide analysis of alternative splicing events in lung adenocarcinoma. We found that 2369 of the 17 800 core Refseq genes appear to have alternative transcripts that are differentially expressed in lung adenocarcinoma versus normal. According to their known functions the largest subset of these genes (30.8%) is believed to be cancer related. Detailed analysis was performed for several genes using PCR, quantitative RT-PCR and DNA sequencing. We found overexpression of ERG variant 2 but not variant 1 in lung tumors and overexpression of CEACAM1 variant 1 but not variant 2 in lung tumors but not in breast or colon tumors. We also identified a novel, overexpressed variant of CDH3 and verified the existence and overexpression of a novel variant of P16 transcribed from the CDKN2A locus. These findings demonstrate how analysis of alternative pre-mRNA processing can shed additional light on differences between tumors and normal tissues as well as between different tumor types. Such studies may lead to the development of additional tools for tumor diagnosis, prognosis and therapy.
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影响因子：
15.9
作者：
Conacci-Sorrell, M;Zhurinsky, J;Ben-Ze'ev, A
通讯作者：
Ben-Ze'ev, A
影响因子：
8
作者：
Gayther, SA;Barski, P;Caldas, C
通讯作者：
Caldas, C
影响因子：
82.9
作者：
Beer, DG;Kardia, SLR;Hanash, S
通讯作者：
Hanash, S
影响因子：
6.3
作者：
Ito, T;Nishida, N;Nakao, K
通讯作者：
Nakao, K
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP