Computational analysis of TP53 mutational landscape unveils key prognostic signatures and distinct pathobiological pathways in head and neck squamous cell cancer.
Computational analysis of TP53 mutational landscape unveils key prognostic signatures and distinct pathobiological pathways in head and neck squamous cell cancer.
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DOI：
10.1038/s41416-020-0984-6
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发表时间：
2020-10
影响因子：
8.8
通讯作者：
Lo Muzio L
中科院分区：
文献类型：
--
作者：
Caponio VCA;Troiano G;Adipietro I;Zhurakivska K;Arena C;Mangieri D;Mascitti M;Cirillo N;Lo Muzio L
肿瘤抑制基因TP 53的突变是头颈部鳞状细胞癌（HNSCC）中最常见的体细胞基因组改变。然而，目前尚不清楚特定的TP 53突变是否在不同的HNSCC亚组中具有不同的临床和病理生理学意义。对癌症基因组图谱（TCGA）上的415例HNSCC病例进行了TP 53突变的系统生物信息学评估。分析了以下特征并与已知的临床病理学变量相关：TP 53的突变谱、位置（在p53蛋白的二级结构和预测结构域内）和众所周知的热点突变。相互作用组-基因组-转录组网络分析突出了不同的基因网络。根据患者的总生存期，生成了一种算法来开发一种新的预后分类系统。TP 53突变在不同解剖部位的HNSCCs中表现出明显的差异。TP 53基因突变是影响HNSCC预后的独立因素。在TCGA HNSCC数据库中，通过我们的新分类算法鉴定的死亡突变的高风险是独立的预后因素。最后，网络分析表明，不同的p53分子通路存在于一个网站和突变特异性的方式。TP 53的突变谱可能作为HNSCC患者的独立预后因素，并且与独特的位点特异性生物网络相关。
Mutations of the tumour-suppressor gene TP53 are the most frequent somatic genomic alterations in head and neck squamous cell carcinoma (HNSCC). However, it is not yet clear whether specific TP53 mutations bear distinct clinical and pathophysiological significance in different HNSCC subgroups. A systematic bioinformatics appraisal of TP53 mutations was performed on 415 HNSCC cases available on The Cancer Genome Atlas (TCGA). The following features were analysed and correlated with known clinicopathological variables: mutational profile of TP53, location (within secondary structure and predicted domains of p53 protein) and well-known hotspot mutations. Interactome–genome–transcriptome network analysis highlighted different gene networks. An algorithm was generated to develop a new prognostic classification system based on patients’ overall survival. TP53 mutations in HNSCCs exhibited distinct differences in different anatomical sites. The mutational profile of TP53 was an independent prognostic factor in HNSCC. High risk of death mutations, identified by our novel classification algorithm, was an independent prognostic factor in TCGA HNSCC database. Finally, network analysis suggested that distinct p53 molecular pathways exist in a site- and mutation-specific manner. The mutational profile of TP53 may serve as an independent prognostic factor in HNSCC patients, and is associated with distinctive site-specific biological networks.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
1.2
作者：
Gu J;Zhou Y;Huang L;Ou W;Wu J;Li S;Xu J;Feng J;Liu B
通讯作者：
Liu B
DOI：
10.1016/j.str.2009.11.011
发表时间：
2010-02-10
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Chen Y;Dey R;Chen L
通讯作者：
Chen L
影响因子：
11.2
作者：
Leroy B;Ballinger ML;Baran-Marszak F;Bond GL;Braithwaite A;Concin N;Donehower LA;El-Deiry WS;Fenaux P;Gaidano G;Langerød A;Hellstrom-Lindberg E;Iggo R;Lehmann-Che J;Mai PL;Malkin D;Moll UM;Myers JN;Nichols KE;Pospisilova S;Ashton-Prolla P;Rossi D;Savage SA;Strong LC;Tonin PN;Zeillinger R;Zenz T;Fraumeni JF Jr;Taschner PE;Hainaut P;Soussi T
通讯作者：
Soussi T
影响因子：
11.5
作者：
Chung, Christine H.;Gillison, Maura L.
通讯作者：
Gillison, Maura L.