Establishment and characterization of a clear cell odontogenic carcinoma cell line with EWSR1-ATF1 fusion gene

Publication date: June 2017
Source:Oral Oncology, Volume 69
Author(s): Satoko Kujiraoka, Takaaki Tsunematsu, Yukiko Sato, Maki Yoshida, Ayataka Ishikawa, Rei Tohyama, Michio Tanaka, Yutaka Kobayashi, Tomoyuki Kondo, Aya Ushio, Kunihiro Otsuka, Mie Kurosawa, Masako Saito, Akiko Yamada, Rieko Arakaki, Hirokazu Nagai, Hiromasa Nikai, Kengo Takeuchi, Toshitaka Nagao, Youji Miyamoto, Naozumi Ishimaru, Yasusei Kudo
ObjectiveClear cell odontogenic carcinoma (CCOC) is a rare malignant odontogenic tumor (MOT) characterized by sheets and lobules of vacuolated and clear cells. To understand the biology of CCOC, we established a new cell line, CCOC-T, with EWSR1-ATF1 fusion gene from a mandible tumor with distant metastasis and characterized this cell line.Materials and methodsTo detect the EWSR1-ATF1 fusion gene, we used three CCOC cases, including the present case, by RT-PCR and FISH analysis. We characterized established CCOC-T cells by checking cell growth, invasion and the expression of odontogenic factors and bone-related factors. Moreover, the gene expression profile of CCOC-T cells was examined by microarray analysis.ResultsHistologically, the primary tumor was comprised of cords and nests containing clear and squamoid cells separated by fibrous septa. In addition, ameloblastomatous islands with palisaded peripheral cells were observed, indicating probable odontogenic origin. This tumor expressed the fusion gene EWSR1-ATF1, which underlies the etiology of hyalinizing clear cell carcinoma (HCCC) and potentially that of CCOC. We found a breakpoint in the EWSR1-ATF1 fusion to be the same as that reported in HCCC. Established CCOC-T cells grew extremely slowly, but the cells showed highly invasive activity. Moreover, CCOC-T cells expressed bone-related molecules, odontogenic factors, and epithelial mesenchymal transition (EMT)-related molecules.ConclusionTo the best of our knowledge, this is the first report on the establishment of a CCOC cell line. CCOC-T cells serve as a useful in vitro model for understanding the pathogenesis and nature of MOT.



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