Head & neck · 2019
Intratumor genetic heterogeneity in squamous cell carcinoma of the oral cavity.
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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
Аннотация
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.
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.