Promoter methylation of TRIM9 as a marker for detection of circulating tumor DNA in breast cancer patients

作者：Mishima Chieko; Kagara Naofumi^*; Matsui Saki; Tanei Tomonori; Naoi Yasuto; Shimoda Masafumi; Shimomura Atsushi; Shimazu Kenzo; Kim Seung Jin; Noguchi Shinzaburo

来源：SpringerPlus, 2015, 4(1): 635.

DOI：10.1186/s40064-015-1423-7

• Breast cancer
• TRIM9
• Methylation
• Biomarker

The aim of the present study was to investigate the promoter methylation status of TRIM9 in breast cancer and to determine the presence of TRIM9-methylated circulating tumor DNA (ctDNA) in plasma. Bisulfite sequencing with a next generation sequencer showed TRIM9 promoter methylation in 92 % (11/12) of breast cancer cell lines (BCCs) and 68 % (13/19) of breast tumor tissues but not in any normal breast tissues (0/19). Methylation ratio of TRIM9 was significantly lower in basal type (9 %, n = 23) than luminal A (69 %, n = 29, P = 0.0003). Quantitative RT-PCR of BCCs disclosed an inverse correlation between TRIM9 mRNA expression and methylation ratio. TRIM9 methylated ctDNA in plasma was detected in 18 % (10/56) of metastatic breast cancer patients but not in any of 60 healthy controls. These results indicate that TRIM9 promoter hypermethylation, which suppresses TRIM9 mRNA expression, occurs in a significant proportion of breast tumors, and that TRIM9-methylated ctDNA thus may serve as a tumor marker for breast cancer.

• 出版日期2015-10-22