Dan P Zandberg1, Luke J Tallon2, Sushma Nagaraj2, Lisa K Sadzewicz2, Yuji Zhang3, Maxwell B Strome4, Xuechu E Zhao2, Kranthi Vavikolanu2, Xiaoyu Zhang5, John C Papadimitriou6, Fleesie A Hubbard5, Søren M Bentzen3, Scott E Strome5, Claire M Fraser2. 1. Department of Hematology/Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania. 2. Department of Medicine, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland. 3. Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland. 4. College of Literature, Science, and the Arts, University of Michigan, Ann Arbor, Michigan. 5. Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, Maryland. 6. Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland.
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.
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.
Authors: Rebecca G Nowak; Søren M Bentzen; Lisa M Schumaker; Nicholas P Ambulos; Nicaise Ndembi; Wuese Dauda; Andrew Mitchell; Trevor J Mathias; Trevor A Crowell; Stefan D Baral; William A Blattner; Manhattan E Charurat; Joel M Palefsky; Kevin J Cullen Journal: Sex Transm Dis Date: 2022-04-01 Impact factor: 2.830