Intratumor genetic heterogeneity in squamous cell carcinoma of the oral cavity

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 w...

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Published inHead & neck Vol. 41; no. 8; pp. 2514 - 2524
Main Authors 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.
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.08.2019
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Abstract 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.
AbstractList 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. 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. 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. These data highlight the challenges to characterization of the mutational landscape of OCC with single site biopsy and have implications for personalized medicine.
BackgroundWe 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.MethodsWe 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.ResultsWe 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.ConclusionThese data highlight the challenges to characterization of the mutational landscape of OCC with single site biopsy and have implications for personalized medicine.
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.
Author Sadzewicz, Lisa K.
Fraser, Claire M.
Hubbard, Fleesie A.
Papadimitriou, John C.
Zhang, Yuji
Zhang, Xiaoyu
Vavikolanu, Kranthi
Strome, Maxwell B.
Bentzen, Søren M.
Tallon, Luke J.
Strome, Scott E.
Zandberg, Dan P.
Zhao, Xuechu E.
Nagaraj, Sushma
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  organization: Institute for Genome Sciences, University of Maryland School of Medicine
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heterogeneity
squamous cell carcinoma
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Snippet Background We sought to evaluate intratumor heterogeneity in squamous cell carcinoma of the oral cavity (OCC) and specifically determine the effect of physical...
We sought to evaluate intratumor heterogeneity in squamous cell carcinoma of the oral cavity (OCC) and specifically determine the effect of physical separation...
BackgroundWe sought to evaluate intratumor heterogeneity in squamous cell carcinoma of the oral cavity (OCC) and specifically determine the effect of physical...
BACKGROUNDWe sought to evaluate intratumor heterogeneity in squamous cell carcinoma of the oral cavity (OCC) and specifically determine the effect of physical...
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SubjectTerms Biopsy
genetic
Head & neck cancer
heterogeneity
Mutation
Neck
Oral cavity
p53 Protein
Parenchyma
Precision medicine
SCCHN
Squamous cell carcinoma
Tumors
Title Intratumor genetic heterogeneity in squamous cell carcinoma of the oral cavity
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fhed.25719
https://www.ncbi.nlm.nih.gov/pubmed/30869813
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