title: Overexpression of A613T and G462T variants of DNA polymerase β weakens chemotherapy sensitivity in esophageal cancer cell lines.
abstract: BACKGROUND
  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.
  
  
  METHODS
  We evaluated the mutation of polβ in a larger cohort of esophageal cancer (EC) patients by RT-PCR and sequencing analysis. The function of the mutation was evaluated by CCK-8, in vivo tumor growth, and flow cytometry assays.
  
  
  RESULTS
  There are 229 patients with the polβ mutation, 18 patients with A613T mutation, 12 patients with G462T mutation among 538 ECs. Analysis results of survival time showed that EC patients with A613T, G462T mutation had a shorter survival than the others (P< 0.05). CCK-8 and flow cytometry assays results showed the A613T, G462T EC9706 cells were less sensitive than WT cells to 5-FU and cisplatin (P< 0.05). Experiments results in vivo showed that the tumor sizes of A613T and G462T group were larger than WT and polβ-/-groups (P< 0.05).
  
  
  CONCLUSIONS
  In this study, we discovered A to T point mutation at nucleotide 613 (A613T) and G to T point mutation at nucleotide 462 (G462T) in the polβ gene through 538 EC patients cohort study. A613T and G462T variant of DNA polymerase β weaken chemotherapy sensitivity of esophageal cancer.
authors.affiliation: School of Basic Medical Sciences, Zhengzhou University, No.100 Kexue Road, 450001 Zhengzhou, Henan China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Basic Medical Sciences, Zhengzhou University, No.100 Kexue Road, 450001 Zhengzhou, Henan China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Basic Medical Sciences, Zhengzhou University, No.100 Kexue Road, 450001 Zhengzhou, Henan China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Sun
authors.affiliation: School of Basic Medical Sciences, Zhengzhou University, No.100 Kexue Road, 450001 Zhengzhou, Henan China.
authors.forename: Wenqiao
authors.initials: W
authors.lastname: Zang
authors.affiliation: School of Basic Medical Sciences, Zhengzhou University, No.100 Kexue Road, 450001 Zhengzhou, Henan China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Basic Medical Sciences, Zhengzhou University, No.100 Kexue Road, 450001 Zhengzhou, Henan China.|Collaborative Innovation Center of Cancer Chemoprevention of Henan, 450001 Zhengzhou, Henan China.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Dong
authors.affiliation: School of Basic Medical Sciences, Zhengzhou University, No.100 Kexue Road, 450001 Zhengzhou, Henan China.|Collaborative Innovation Center of Cancer Chemoprevention of Henan, 450001 Zhengzhou, Henan China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Zhao
keywords: Chemotherapy sensitivity; DNA polymerase β; Esophageal cancer; Mutation