High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma.
High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma.
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DOI：
10.1158/1078-0432.ccr-17-0721
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发表时间：
2018-04-01
期刊：
影响因子：
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通讯作者：
Pickering CR
中科院分区：
文献类型：
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作者：
Sandulache VC;Michikawa C;Kataria P;Gleber-Netto FO;Bell D;Trivedi S;Rao X;Wang J;Zhao M;Jasser S;Myers JN;Pickering CR
结外延伸（ENE）的发展与口腔鳞状细胞癌（OSCC）患者的低生存率相关。在这里，我们试图确认ENE作为一个不良预后因素的作用，并确定ENE的基因组和表观遗传标记，以建立预测模型和改进治疗选择。一个机构队列（德克萨斯大学MD安德森癌症中心）被用来确认ENE对临床结果的影响，并评估原发组织和含有ENE的组织的基因组特征。我们分析了来自癌症基因组图谱（TCGA）的OSCC数据，以确定是否存在与淋巴结和ENE状态相关的分子事件。ENE与总生存率和无病生存率降低有关。TP53基因突变是ENE+ OSCC中最常见的事件。与ENE-肿瘤相比，ENE+肿瘤中TP53突变的频率更高，野生型（wt） TP53在pN0肿瘤中高度代表。pN+ENE+患者TP53高危突变比例最高。原发性肿瘤（PT）和淋巴结伴ENE （LN）均表现出较高的TP53突变率（分别为58.8%和58.8%），两个组织部位的等位基因频率无显著变化。ENE是OSCC、OS和DFS最重要的标志物之一。与TP53基因的高风险突变相关的更具侵略性的生物表型发生了转变。需要前瞻性临床试验来确定TP53突变状态是否可以用于个性化治疗决策。
Development of extra-nodal extension (ENE) has been associated with poor survival in patients with oral cavity squamous cell carcinoma (OSCC). Here we sought to confirm the role of ENE as a poor prognostic factor, and identify genomic and epigenetic markers of ENE in order to develop a predictive model and improve treatment selection. An institutional cohort (University of Texas MD Anderson Cancer Center) was utilized to confirm the impact of ENE on clinical outcomes and evaluate the genomic signature of primary and ENE containing tissue. OSCC data from The Cancer Genome Atlas (TCGA) were analyzed for the presence of molecular events associated with nodal and ENE status. ENE was associated with decreased overall and disease free survival. Mutation of the TP53 gene was the most common event in ENE+ OSCC. The frequency of TP53 mutation in ENE+ tumors was higher compared to ENE- tumors and wild-type (wt) TP53 was highly-represented in pN0 tumors. pN+ENE+ patients had the highest proportion of high-risk TP53 mutations. Both primary tumors (PT) and lymph nodes with ENE (LN) exhibited a high rate of TP53 mutations (58.8%, 58.8% respectively) with no significant change in allele frequency between the two tissue sites. ENE is one of the most significant markers of OSCC OS and DFS. There is a shift toward a more aggressive biological phenotype associated with high-risk mutations of the TP53 gene. Prospective clinical trials are required to determine whether TP53 mutational status can be used for personalized treatment decisions.