Frequent mutation related with overexpression of DNA polymerase beta in primary tumors and precancerous lesions of human stomach

Abstract 

To explore whether DNA polymerase beta (pol β) contributes to the malignant transformation of gastric mucosa, we examined pol β in gastric tumor cell lines, primary tumors and precancerous lesions. Point mutations of pol β were detected in 6 of 13 cell lines and 23 of 104 tissues including 35.0% (14/40) of gastric cancer (GC), 30.0% (3/10) of dysplasia (Dys), 28.6% (4/14) of intestinal metaplasia (IM) and 10.5% (2/19) of chronic atrophic gastritis (CAG), respectively. A frequent mutation was a T to C transition at nucleotide 889, which was observed in 4 GC cell lines, 7 GC, 2 Dys, and 2 IM. The level of pol β expression in tumors was higher than that of their matched normal tissues and gradual changes from GC, Dys, CAG to IM. These results indicate that the mutation and overexpression of pol β may influence the progression during gastric carcinogenesis.

Keywords: Gastric cancer, Precancerous lesions, DNA polymerase beta, BER, Mutation