口腔鳞状细胞癌的肿瘤内基因异质性
Intratumor genetic heterogeneity in squamous cell carcinoma of the oral cavity.
作者信息
Zandberg Dan P, Tallon Luke J, Nagaraj Sushma, Sadzewicz Lisa K, Zhang Yuji, Strome Maxwell B, Zhao Xuechu E, Vavikolanu Kranthi, Zhang Xiaoyu, Papadimitriou John C, Hubbard Fleesie A, Bentzen Søren M, Strome Scott E, Fraser Claire M
机构信息
Department of Hematology/Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania.
Department of Medicine, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland.
出版信息
Head Neck. 2019 Aug;41(8):2514-2524. doi: 10.1002/hed.25719. Epub 2019 Mar 14.
BACKGROUND
We sought to evaluate intratumor heterogeneity in squamous cell carcinoma of the oral cavity (OCC) and specifically determine the effect of physical separation and histologic differentiation within the same tumor.
METHODS
We performed whole exome sequencing on five biopsy sites-two from well-differentiated, two from poorly differentiated regions, and one from normal parenchyma-from five primary OCC specimens.
RESULTS
We found high levels of intratumor heterogeneity and, in four primary tumors, identified only 0 to 2 identical mutations in all subsites. We found that the heterogeneity inversely correlated with physical separation and that pairs of well-differentiated samples were more similar to each other than analogous poorly differentiated specimens. Only TP53 mutations, but not other purported "driver mutations" in head and neck squamous cell carcinoma, were found in multiple biopsy sites.
CONCLUSION
These data highlight the challenges to characterization of the mutational landscape of OCC with single site biopsy and have implications for personalized medicine.
背景
我们试图评估口腔鳞状细胞癌（OCC）的肿瘤内异质性，并特别确定同一肿瘤内物理分离和组织学分化的影响。
方法
我们对来自五个原发性OCC标本的五个活检部位进行了全外显子组测序，其中两个来自高分化区域，两个来自低分化区域，一个来自正常实质组织。
结果
我们发现肿瘤内异质性水平很高，并且在四个原发性肿瘤中，所有亚部位仅鉴定出0至2个相同的突变。我们发现异质性与物理分离呈负相关，并且高分化样本对彼此之间的相似性高于类似的低分化标本。在多个活检部位仅发现了TP53突变，而在头颈部鳞状细胞癌中未发现其他所谓的“驱动突变”。
结论
这些数据凸显了通过单部位活检来表征OCC突变图谱的挑战，并对个性化医疗具有启示意义。
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