Tumor-specific mutation and downregulation of ING5 detected in oral squamous cell carcinoma
Beyhan Cengiz
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-5-1, Okayama, Japan
Department of Physiology, Faculty of Medicine, University of Gaziantep, Universite Bulvari, Tip Fakultesi Prof. Dr. Sabri Gungor Arastirma Merkezi, Gaziantep, Turkey
Search for more papers by this authorEsra Gunduz
Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-5-1, Okayama, Japan
Department of Medical Genetics, Faculty of Medicine, Fatih University, Alparslan Turkes Cad. No: 57 Emek, Ankara, Turkey
Search for more papers by this authorCorresponding Author
Mehmet Gunduz
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-5-1, Okayama, Japan
Department of Otolaryngology Head and Neck Surgery, Wakayama Medical University, 811-1, Kimiidera, Wakayama, Japan
Fax: +81-86-235-6654
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayamashi 700-8558, JapanSearch for more papers by this authorLevent Bekir Beder
Department of Otolaryngology Head and Neck Surgery, Wakayama Medical University, 811-1, Kimiidera, Wakayama, Japan
Search for more papers by this authorRyo Tamamura
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-5-1, Okayama, Japan
Search for more papers by this authorCahit Bagci
Department of Physiology, Faculty of Medicine, University of Gaziantep, Universite Bulvari, Tip Fakultesi Prof. Dr. Sabri Gungor Arastirma Merkezi, Gaziantep, Turkey
Search for more papers by this authorNoboru Yamanaka
Department of Otolaryngology Head and Neck Surgery, Wakayama Medical University, 811-1, Kimiidera, Wakayama, Japan
Search for more papers by this authorKenji Shimizu
Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-5-1, Okayama, Japan
Search for more papers by this authorHitoshi Nagatsuka
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-5-1, Okayama, Japan
Search for more papers by this authorBeyhan Cengiz
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-5-1, Okayama, Japan
Department of Physiology, Faculty of Medicine, University of Gaziantep, Universite Bulvari, Tip Fakultesi Prof. Dr. Sabri Gungor Arastirma Merkezi, Gaziantep, Turkey
Search for more papers by this authorEsra Gunduz
Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-5-1, Okayama, Japan
Department of Medical Genetics, Faculty of Medicine, Fatih University, Alparslan Turkes Cad. No: 57 Emek, Ankara, Turkey
Search for more papers by this authorCorresponding Author
Mehmet Gunduz
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-5-1, Okayama, Japan
Department of Otolaryngology Head and Neck Surgery, Wakayama Medical University, 811-1, Kimiidera, Wakayama, Japan
Fax: +81-86-235-6654
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayamashi 700-8558, JapanSearch for more papers by this authorLevent Bekir Beder
Department of Otolaryngology Head and Neck Surgery, Wakayama Medical University, 811-1, Kimiidera, Wakayama, Japan
Search for more papers by this authorRyo Tamamura
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-5-1, Okayama, Japan
Search for more papers by this authorCahit Bagci
Department of Physiology, Faculty of Medicine, University of Gaziantep, Universite Bulvari, Tip Fakultesi Prof. Dr. Sabri Gungor Arastirma Merkezi, Gaziantep, Turkey
Search for more papers by this authorNoboru Yamanaka
Department of Otolaryngology Head and Neck Surgery, Wakayama Medical University, 811-1, Kimiidera, Wakayama, Japan
Search for more papers by this authorKenji Shimizu
Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-5-1, Okayama, Japan
Search for more papers by this authorHitoshi Nagatsuka
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-5-1, Okayama, Japan
Search for more papers by this authorAbstract
Our previous study showed high frequency of allelic loss at chromosome 2q37 region in oral cancer. This location contains several candidate tumor suppressor genes such as PPP1R7, ILKAP, DTYMK and ING5. We previously showed 3 members of inhibitor of growth (ING) family, ING1, ING3 and ING4 as tumor suppressor gene in head and neck cancer. As ING5 shows high homology with other members of ING genes including highly conserved carboxy-terminal plant homeodomain and nuclear localization signal, we first picked up ING5 and examined it as a possible tumor suppressor in oral cancer. For this aim, mutation and mRNA expression status of ING5 in paired normal and oral squamous cell carcinoma samples were examined by reverse transcription polymerase chain reaction (RT-PCR) and sequencing. Three missense mutations located within leucine zipper like (LZL) finger and novel conserved region (NCR) domains in ING5 protein were detected, probably abrogating its normal function. We also found 5 different alternative splicing variants of ING5. Then, we examined mRNA level of ING5 by quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) analysis, which demonstrated decreased expression of ING5 mRNA in 61% of the primary tumors as compared to the matched normal samples. In conclusion, tumor-specific mutation and downregulation of ING5 mRNA suggested it as a tumor suppressor gene in oral squamous cell carcinoma.
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