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Genomic Profiling of Oral Squamous Cell Carcinoma by Array-Based Comparative Genomic Hybridization
Authors:Shunichi Yoshioka  Yoshiyuki Tsukamoto  Naoki Hijiya  Chisato Nakada  Tomohisa Uchida  Keiko Matsuura  Ichiro Takeuchi  Masao Seto  Kenji Kawano  Masatsugu Moriyama
Affiliation:1. Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan.; 2. Department of Dentistry and Oral-Maxillo-Facial Surgery, Oita, Japan, Faculty of Medicine, Oita University, Oita, Japan.; 3. Department of Computer Science/Scientific and Engineering Simulation, Nagoya Institute of Technology, Nagoya, Japan.; 4. Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.; Deutsches Krebsforschungszentrum, Germany,
Abstract:We designed a study to investigate genetic relationships between primary tumors of oral squamous cell carcinoma (OSCC) and their lymph node metastases, and to identify genomic copy number aberrations (CNAs) related to lymph node metastasis. For this purpose, we collected a total of 42 tumor samples from 25 patients and analyzed their genomic profiles by array-based comparative genomic hybridization. We then compared the genetic profiles of metastatic primary tumors (MPTs) with their paired lymph node metastases (LNMs), and also those of LNMs with non-metastatic primary tumors (NMPTs). Firstly, we found that although there were some distinctive differences in the patterns of genomic profiles between MPTs and their paired LNMs, the paired samples shared similar genomic aberration patterns in each case. Unsupervised hierarchical clustering analysis grouped together 12 of the 15 MPT-LNM pairs. Furthermore, similarity scores between paired samples were significantly higher than those between non-paired samples. These results suggested that MPTs and their paired LNMs are composed predominantly of genetically clonal tumor cells, while minor populations with different CNAs may also exist in metastatic OSCCs. Secondly, to identify CNAs related to lymph node metastasis, we compared CNAs between grouped samples of MPTs and LNMs, but were unable to find any CNAs that were more common in LNMs. Finally, we hypothesized that subpopulations carrying metastasis-related CNAs might be present in both the MPT and LNM. Accordingly, we compared CNAs between NMPTs and LNMs, and found that gains of 7p, 8q and 17q were more common in the latter than in the former, suggesting that these CNAs may be involved in lymph node metastasis of OSCC. In conclusion, our data suggest that in OSCCs showing metastasis, the primary and metastatic tumors share similar genomic profiles, and that cells in the primary tumor may tend to metastasize after acquiring metastasis-associated CNAs.
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