| Literature DB >> 26880326 |
Keisuke Kosumi1, Yoshifumi Baba1, Takatsugu Ishimoto1, Kazuto Harada1, Kenichi Nakamura1, Mayuko Ohuchi1, Yuki Kiyozumi1, Daisuke Izumi1, Ryuma Tokunaga1, Katsunobu Taki1, Takaaki Higashi1, Tatsunori Miyata1, Hironobu Shigaki1, Junji Kurashige1, Yukiharu Hiyoshi1, Masaaki Iwatsuki1, Shiro Iwagami1, Yasuo Sakamoto1, Yuji Miyamoto1, Naoya Yoshida1, Eiji Oki2, Masayuki Watanabe3, Hideo Baba4.
Abstract
APOBEC3B belongs to the cytidine deaminase apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC3) family of enzymes and induces C to T transitions of target DNA by cytidine deamination. Recently, several mutations in various cancers have been linked to APOBEC3B, suggesting a crucial role for this protein in carcinogenesis and cancer development. However, the significance of APOBEC3B in esophageal squamous cell carcinoma (ESCC) remains uncertain. In addition, the APOBEC3B immunoreactivity in cancer tissues is uncertain. Recently, we have demonstrated that PIK3CA mutation and the methylation level of long interspersed nucleotide element 1 (LINE-1) (a surrogate marker of global DNA methylation level) are prognostic markers and have crucial role on malignancy in ESCC patients. This study aims to clarify the impact of APOBEC3B on the clinical, pathological, and molecular features of ESCC. We evaluated APOBEC3B expression in ESCC and investigated the relationships among the immunoreactivity of APOBEC3B, clinical and pathological features, and the molecular features of ESCC (PIK3CA mutation, p53 expression, and LINE-1 methylation level). The immunoreactivity and mRNA level of APOBEC3B were significantly higher in cancer tissues than in noncancerous esophageal mucosae (P = 0.050). APOBEC3B expression was significantly correlated with PIK3CA mutation (P = 0.013), particularly with C to T transitions of PIK3CA (P = 0.041). Moreover, a high expression of APOBEC3B was significantly associated with LINE-1 hypomethylation (P = 0.027). Given the crucial roles of PIK3CA mutation and LINE-1 methylation levels, our findings might provide new insights into the biological mechanisms of ESCC tumorigenesis and progression.Entities:
Keywords: APOBEC3B; C > T transition; Esophageal squamous cell carcinoma; LINE-1 methylation level; PIK3CA mutation
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Year: 2016 PMID: 26880326 DOI: 10.1007/s12032-016-0739-7
Source DB: PubMed Journal: Med Oncol ISSN: 1357-0560 Impact factor: 3.064