Satoko Kujiraoka1, Takaaki Tsunematsu1, Yukiko Sato2, Maki Yoshida3, Ayataka Ishikawa4, Rei Tohyama5, Michio Tanaka6, Yutaka Kobayashi7, Tomoyuki Kondo1, Aya Ushio1, Kunihiro Otsuka1, Mie Kurosawa1, Masako Saito1, Akiko Yamada1, Rieko Arakaki1, Hirokazu Nagai8, Hiromasa Nikai9, Kengo Takeuchi2, Toshitaka Nagao3, Youji Miyamoto8, Naozumi Ishimaru10, Yasusei Kudo11. 1. Department of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan. 2. Department of Pathology, Cancer Institute, Japanese Foundation of Cancer Research, Tokyo, Japan. 3. Department of Human Pathology, Tokyo Medical University, Tokyo, Japan. 4. Department of Pathology, Saitama Cancer Center, Saitama, Japan. 5. Department of Clinical Laboratory, Tokyo Medical and Dental University, Dental Hospital, Tokyo, Japan. 6. Department of Pathology, Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan. 7. Department of Oral Surgery, Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan. 8. Department of Oral Surgery, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan. 9. Department of Oral Maxillofacial Pathobiology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. 10. Department of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan. Electronic address: ishimaru.n@tokushima-u.ac.jp. 11. Department of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan. Electronic address: yasusei@tokushima-u.ac.jp.
Abstract
OBJECTIVE: Clear 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 METHODS: To 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. RESULTS: Histologically, 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. CONCLUSION: To 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.
OBJECTIVE:Clear 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 METHODS: To 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. RESULTS: Histologically, 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. CONCLUSION: To 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.
Authors: Erasmo Bernardo Marinho; Ana Paula Negreiros Nunes Alves; Francisco Januário Farias Pereira-Filho; Antonio Ernando Carlos Ferreira-Junior; Mário Rogério Lima Mota; Fabricio Bitu Sousa Journal: Oral Maxillofac Surg Date: 2021-09-20