High intratumor genetic heterogeneity is related to worse outcome in patients with head and neck squamous cell carcinoma.
High intratumor genetic heterogeneity is related to worse outcome in patients with head and neck squamous cell carcinoma.
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DOI：
10.1002/cncr.28150
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发表时间：
2013-08-15
期刊：
影响因子：
6.2
通讯作者：
Rocco, James W.
中科院分区：
文献类型：
--
作者：
Mroz, Edmund A.;Tward, Aaron D.;Pickering, Curtis R.;Myers, Jeffrey N.;Ferris, Robert L.;Rocco, James W.
关键词：
尽管个体患者肿瘤中存在遗传异质性已被证实，但目前尚不清楚更大的异质性是否预示着更糟糕的结果。一种基于下一代测序(NGS)数据的遗传异质性的定量度量，突变-等位基因肿瘤异质性(MATH)，以前被开发并应用于头颈部鳞状细胞癌(HNSCC)的数据集。这一指标是否与临床结果相关，此前并未进行评估。我们研究了74例完成外显子组测序的HNSCC患者的MAX与临床、病理和总生存期数据的相关性。高数学(高于中位数的数学数值)与较短的总生存期显著相关(风险比2.5；95%CI，1.3至4.8)。在晚期临床高危患者以及根据已验证的生物标记物归类为高风险的肿瘤中，包括那些人乳头瘤病毒阴性或具有破坏性TP53突变的肿瘤，MAX与不良结局类似。在接受化疗的患者中，高数学风险比为4.1(95%CI：1.6至10.2)。这一肿瘤遗传异质性的新指标与肿瘤进展和不良治疗结果显著相关，支持了遗传异质性较高预示着HNSCC临床结果较差的假设。一些已知生物标记物的预后价值可能是它们与高度遗传异质性相关的结果。MATH为这种异质性提供了一种有用的衡量标准，随着来自同质治疗的患者队列的NGS数据变得可用，它将被前瞻性地验证。
Although the presence of genetic heterogeneity within individual patients’ tumors is established, it is unclear whether greater heterogeneity predicts worse outcome. A quantitative measure of genetic heterogeneity based on next-generation sequencing (NGS) data, mutant-allele tumor heterogeneity (MATH), was previously developed and applied to a data set on head and neck squamous cell cancer (HNSCC). Whether this measure correlates with clinical outcome was not previously assessed. We examined the association of MATH with clinical, pathological and overall-survival data for 74 HNSCC patients for whom exome sequencing was completed. High MATH (a MATH value above the median) was significantly associated with shorter overall survival (hazard ratio 2.5; 95% CI, 1.3 to 4.8). MATH was similarly associated with adverse outcomes in clinically high risk patients with advanced stage, and in tumors classified as high risk on the basis of validated biomarkers including those negative for human papillomavirus or having disruptive TP53 mutations. In patients who received chemotherapy, the hazard ratio for high MATH was 4.1 (95%CI: 1.6 to 10.2). This novel measure of tumor genetic heterogeneity is significantly associated with tumor progression and adverse treatment outcomes, supporting the hypothesis that higher genetic heterogeneity portends worse clinical outcome in HNSCC. The prognostic value of some known biomarkers may be the result of their association with high genetic heterogeneity. MATH provides a useful measure of that heterogeneity, to be prospectively validated as NGS data from homogeneously treated patient cohorts becomes available.
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影响因子：
4.8
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