Abstract P2-05-03: Clinical implication of APOBEC3A and 3B in Korean patients with breast cancer

Abstract

Abstract Background: Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) family is known to function in innate immune system that protects against retrovirus by deaminating cytosine to uracil in single-stranded DNA. APOBEC family has emerged as an endogenous mutator to contribute to the mutation burden in many cancers. We aimed to evaluate the expression of APOBEC3A (A3A), 3B (A3B) mRNA and APOBEC3A-3B deletion polymorphism in Korean breast cancer patients and investigate the correlation between their expression and clinicopathological characteristics. Methods: One hundred thirty-eight patients who underwent surgery for breast cancer in Uijeongbu St. Mary's Hospital between January 2013 and December 2016 were evaluated. RNA and DNA were extracted from 138 breast cancer tissues and 10 adjacent normal breast tissues. The levels of A3A and A3B mRNA transcripts were determined using real-time quantitative PCR. Insertion and deletion PCR assays were performed to detect the APOBEC3A-3B deletion allele. Mutation hotspots in exon 2-11 of TP53 and exon 9/20 of PIK3CA were evaluated using direct sequencing method. Results: The expression of A3B was increased in breast cancer tissues than in normal breast tissues. The median A3B mRNA expression levels in both triple-negative breast cancer and human epidermal growth factor 2-positive breast cancer were significantly higher than in hormone receptor-positive breast cancer. Old age and high ki-67 expression were associated with increased expression of A3A and A3B. Advanced stage, presence of lymph node involvement, and high histological grade were associated with increased expression of A3A. The APOBEC3B deletion allele was found in 78 (56%) tumor samples. There was no significant association between A3A, A3B mRNA levels and the presence of APOBEC3B deletion allele. There was no difference in clinicopathological characteristics according to the presence of APOBEC3B deletion allele except histological grade. The frequency of high histological grade was significantly higher in tumors with APOBEC3B deletion allele than tumors without APOBEC3B deletion allele. TP53 mutations were identified in 12 (8.7%) cases and PIK3CA mutations were identified in 31 (22.5%) cases. There were no significant differences in the levels of A3A and A3B mRNA expression by TP53 mutation status. The presence of a PIK3CA mutation was significantly associated with lower A3A expression. Conclusions: The levels of A3B mRNA expression showed a difference according to breast cancer subtype, and triple-negative breast cancer showed the highest levels of A3B mRNA expression. The high levels of A3A and A3B mRNA expression were associated with an aggressive phenotype including high proliferation index. The APOBEC3A-3B deletion polymorphism was found in about half of the patients, but there was no difference in clinicopathological factors according to the presence of APOBEC3B deletion allele except histological grade. Citation Format: Won HS, Sun DS, Ko YH, You SH, Kim YS, Kim JS. Clinical implication of APOBEC3A and 3B in Korean patients with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-05-03.