Genome-wide expression and copy number analysis identifies driver genes in gingivobuccal cancers.
Genome-wide expression and copy number analysis identifies driver genes in gingivobuccal cancers.
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全基因组表达和拷贝数分析标识了牙龈癌中的驱动基因。
DOI：
10.1002/gcc.20940
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发表时间：
2012-02
影响因子：
3.7
通讯作者：
Mahimkar, Manoj B.
中科院分区：
文献类型：
--
作者：
Ambatipudi, Srikant;Gerstung, Moritz;Pandey, Manishkumar;Samant, Tanuja;Patil, Asawari;Kane, Shubhada;Desai, Rajiv S.;Schaeffer, Alejandro A.;Beerenwinkel, Niko;Mahimkar, Manoj B.
牙龈颊复合体（GBC）癌（口腔癌的一个亚部位，包括颊粘膜、龈颊沟、下牙龈区域和磨牙后三角区）发生和进展的分子机制仍然知之甚少。识别 GBC 癌症相关基因表达特征和位于改变的染色体区域的驱动基因对于理解其发病机制的分子基础至关重要。对 27 种具有已知染色体改变的 GBC 癌症进行全基因组表达谱分析，以揭示差异表达的基因。通过整合拷贝数和基因表达数据来鉴定推定的驱动基因。共发现315个基因存在差异表达（P≤0.05，logFC>2.0），其中11个基因通过实时定量逆转录酶PCR（qRT-PCR）在肿瘤（n=57）和正常GBC组织（n=18）中得到验证。通过免疫组织化学 (IHC) 分析验证了染色体带 8q24.3 中 LY6K 的过度表达。我们发现，位于反复染色体改变区域的基因中有 78.5% (2,417/3,079) 显示出拷贝数依赖性表达，表明拷贝数改变对整体基因表达有直接影响。综合分析显示 11q22.2 中的 BIRC3 是与不良临床结果相关的候选驱动基因。我们的研究确定了先前未报告的口腔癌同质亚型中的差异表达基因以及可能导致疾病发生和进展的候选驱动基因。
The molecular mechanisms contributing to the development and progression of gingivobuccal complex (GBC) cancers–a sub-site of oral cancer, comprising the buccal mucosa, the gingivobuccal sulcus, the lower gingival region and the retromolar trigone-remain poorly understood. Identifying the GBC cancer-related gene expression signature and the driver genes residing on the altered chromosomal regions is critical for understanding the molecular basis of its pathogenesis. Genome-wide expression profiling of 27 GBC cancers with known chromosomal alterations was performed to reveal differentially expressed genes. Putative driver genes were identified by integrating copy number and gene expression data. A total of 315 genes were found differentially expressed (P≤0.05, logFC>2.0) of which eleven genes were validated by real-time quantitative reverse transcriptase-PCR (qRT-PCR) in tumors (n=57) and normal GBC tissues (n=18). Overexpression of LY6K, in chromosome band 8q24.3, was validated by immunohistochemical (IHC) analysis. We found that 78.5% (2,417/3,079) of the genes located in regions of recurrent chromosomal alterations show copy number dependent expression indicating that copy number alteration has a direct effect on global gene expression. The integrative analysis revealed BIRC3 in 11q22.2 as a candidate driver gene associated with poor clinical outcome. Our study identified previously unreported differentially expressed genes in a homogeneous subtype of oral cancer and the candidate driver genes that may contribute to the development and progression of the disease.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1177/039463200501800311
发表时间：
2005-07-01
影响因子：
3.5
作者：
Carinci, F;Lo Muzio, L;Pezzetti, F
通讯作者：
Pezzetti, F
影响因子：
8.4
作者：
Grzybowska-Izydorczyk, Olga;Cebula, Barbara;Smolewski, Piotr
通讯作者：
Smolewski, Piotr
影响因子：
4.4
作者：
Gertz, E. Michael;Sengupta, Kundan;Schaeffer, Alejandro A.
通讯作者：
Schaeffer, Alejandro A.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y