AB110. Novel alteration of mitochondrial tRNA^Trp in a group of Vietnamese breast cancer patients

Background and objective: Mitochondria are organelles that generate ATP—required energy for all activities of the cell. Mitochondria have their own genome which encodes for 22 transfer RNAs (tRNAs), 2 ribosomal RNAs (rRNAs) and 13 proteins of oxidative phosphorylation system in the inner membrane. Previous studies have shown that the alterations of mitochondrial DNA were associated with various cancers including breast cancer. In particular, the alterations of mt-tRNA genes were focused because they directly affected the tRNA molecules and the translation, many proteins and different processes. In this study, we analyzed the alterations of some mitochondrial tRNA genes in a group of Vietnamese breast cancer patients to investigate the variants of mt-tRNA genes and their role in breast cancer.

Methods: Total DNA was extracted from pairs of tumor and adjacent tissues (2-3 cm from the tumor) of 30 breast cancer patients collected at Vietnam National Cancer Hospital. The alterations of mt-tRNA genes were determined by using PCR - RFLP and sequencing methods. Bioinformatics tools were used to predict the changes in secondary structure of mutated tRNAs. Data were analyzed by statistical methods.

Results: We did not identify the mutations m.3243A > G of mt-tRNA^Leu(UUR) and m.12300G > A of mt-tRNA^Leu(CUN) in studied samples. However, the sequencing results revealed two variants m.5591G > A and m.5536A > T of mt-tRNA^Ala and mt-tRNA^Trp respectively, in which m.5536A > T (1/30 cases) was a novel alteration that has not been reported so far. Besides, m.5536A > T does alter the structure of tRNA^Trp predicted by bioinformatics tools and affects its function. Moreover, PCR-RPLP analysis also indicated the heteroplasmy of m.5536A > T variant. Further studies have been being conducted to determine the heteroplasmic levels related to this alteration in breast cancer tissues.

Conclusions: It is the first time that alteration m.5536A > T of mt-tRNA^Trp gene has been reported in patients with breast cancer. This alteration may change the normal structure of the tRNA^Trp and affect the function of the molecule.

Keywords: Breast cancer; RCR-RFLP; tRNA^Ala; tRNA^Trp