G648C variant of DNA polymerase β sensitizes esophageal cancer to chemotherapy.
Human DNA polymerase β (polβ) is a small monomeric protein that is essential for short-patch base excision repair. It plays an important role in regulating the sensitivity of tumor cells to chemotherapy. We have previously identified a G to C point mutation at nucleotide 648 (G648C) of polβ in esophageal cancer (EC). In this study, we evaluated the mutation of polβ in a larger cohort of EC patients by RT-PCR and sequencing analysis. The function of the mutation was evaluated by MTT, in vivo tumor growth, and flow cytometry assays. The G648C mutation occurred in 15 (3.45 %) of 435 EC patients. In addition, patients with this mutation had significantly longer survival time than those without, following postoperative chemotherapy. Cell lines with G648C mutation in polβ gene were more sensitive to treatment with 5-fluorouracil and cisplatin than those with wild-type polβ. These results suggest that polβ gene with G648C mutation in surgically resected esophagus may be clinically useful for predicting responsiveness to chemotherapy in patients with EC. The polβ gene alteration may serve as a prognostic biomarker for EC.
College of Basic Medical Sciences, Zhengzhou University, No.100 Kexue Road, Zhengzhou, Henan, 450001, China.|Collaborative Innovation Center of Cancer Chemoprevention of Henan, Zhengzhou, Henan, 450001, China.
Yuanyuan
Y
Wang
College of Basic Medical Sciences, Zhengzhou University, No.100 Kexue Road, Zhengzhou, Henan, 450001, China.
Qianqian
Q
Sun
Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450052, China.
Wei
W
Guo
College of Basic Medical Sciences, Zhengzhou University, No.100 Kexue Road, Zhengzhou, Henan, 450001, China.
Xiaonan
X
Chen
College of Basic Medical Sciences, Zhengzhou University, No.100 Kexue Road, Zhengzhou, Henan, 450001, China.
Yuwen
Y
Du
College of Basic Medical Sciences, Zhengzhou University, No.100 Kexue Road, Zhengzhou, Henan, 450001, China.
Wenqiao
W
Zang
College of Basic Medical Sciences, Zhengzhou University, No.100 Kexue Road, Zhengzhou, Henan, 450001, China.|Collaborative Innovation Center of Cancer Chemoprevention of Henan, Zhengzhou, Henan, 450001, China.
Ziming
Z
Dong
College of Basic Medical Sciences, Zhengzhou University, No.100 Kexue Road, Zhengzhou, Henan, 450001, China. zhaogq@zzu.edu.cn.|Collaborative Innovation Center of Cancer Chemoprevention of Henan, Zhengzhou, Henan, 450001, China. zhaogq@zzu.edu.cn.
Guoqiang
G
Zhao
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D004252:DNA Mutational Analysis; D019951:DNA Polymerase beta / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D019951:DNA Polymerase beta
Chemotherapy; DNA polymerase β; Esophageal cancer; Point mutation