APOBEC3B is an enzymatic source of molecular alterations in esophageal squamous cell carcinoma

作者：Kosumi Keisuke; Baba Yoshifumi; Ishimoto Takatsugu; Harada Kazuto; Nakamura Kenichi; Ohuchi Mayuko; Kiyozumi Yuki; Izumi Daisuke; Tokunaga Ryuma; Taki Katsunobu; Higashi Takaaki; Miyata Tatsunori; Shigaki Hironobu; Kurashige Junji; Hiyoshi Yukiharu; Iwatsuki Masaaki; Iwagami Shiro; Sakamoto Yasuo; Miyamoto Yuji; Yoshida Naoya; Oki Eiji; Watanabe Masayuki; Baba Hideo

来源：Medical Oncology, 2016, 33(3): 26.

DOI：10.1007/s12032-016-0739-7

• APOBEC3B
• PIK3CA mutation
• C > T transition
• Esophageal squamous cell carcinoma
• LINE-1 methylation level

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 non-cancerous 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.

• 出版日期2016-3
• 单位中国医学科学院肿瘤医院