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

Mishima C, Kagara N, Matsui S, Tanei T, Naoi Y, Shimoda M, Shimomura A, Shimazu K, Kim SJ, Noguchi S - Springerplus (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, Osaka 565-0871 Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Association between TRIM9 mRNA expressions obtained with ISH and IHC analysis and methylation ratios in breast cancer tissues. TRIM9 hypermethylated or hypomethylated breast cancer tissues were subjected to ISH (a) and IHC (b) for TRIM9 mRNA. Each immunoreactivity was one of four scores (0, 1+, 2+ and 3+). ISH, in situ hybridization; IHC, immunohistochemistry
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Fig5: Association between TRIM9 mRNA expressions obtained with ISH and IHC analysis and methylation ratios in breast cancer tissues. TRIM9 hypermethylated or hypomethylated breast cancer tissues were subjected to ISH (a) and IHC (b) for TRIM9 mRNA. Each immunoreactivity was one of four scores (0, 1+, 2+ and 3+). ISH, in situ hybridization; IHC, immunohistochemistry

Mentions: Next, to determine whether methylation is related to gene expression, we subjected the TRIM9 hypermethylated (n = 10) and hypomethylated tumors (n = 10) to ISH and IHC and found that neither ISH signals nor IHC scores in tumor cells were significantly associated with methylation ratios (Fig. 5).Fig. 5


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

Mishima C, Kagara N, Matsui S, Tanei T, Naoi Y, Shimoda M, Shimomura A, Shimazu K, Kim SJ, Noguchi S - Springerplus (2015)

Association between TRIM9 mRNA expressions obtained with ISH and IHC analysis and methylation ratios in breast cancer tissues. TRIM9 hypermethylated or hypomethylated breast cancer tissues were subjected to ISH (a) and IHC (b) for TRIM9 mRNA. Each immunoreactivity was one of four scores (0, 1+, 2+ and 3+). ISH, in situ hybridization; IHC, immunohistochemistry
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4627990&req=5

Fig5: Association between TRIM9 mRNA expressions obtained with ISH and IHC analysis and methylation ratios in breast cancer tissues. TRIM9 hypermethylated or hypomethylated breast cancer tissues were subjected to ISH (a) and IHC (b) for TRIM9 mRNA. Each immunoreactivity was one of four scores (0, 1+, 2+ and 3+). ISH, in situ hybridization; IHC, immunohistochemistry
Mentions: Next, to determine whether methylation is related to gene expression, we subjected the TRIM9 hypermethylated (n = 10) and hypomethylated tumors (n = 10) to ISH and IHC and found that neither ISH signals nor IHC scores in tumor cells were significantly associated with methylation ratios (Fig. 5).Fig. 5

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, Osaka 565-0871 Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus