Methylation of the SEPT9_v2 promoter as a novel marker for the detection of circulating tumor DNA in breast cancer patients

  • Authors:
    • Saki Matsui
    • Naofumi Kagara
    • Chieko Mishima
    • Yasuto Naoi
    • Masafumi Shimoda
    • Atsushi Shimomura
    • Kenzo Shimazu
    • Seung Jin Kim
    • Shinzaburo Noguchi
  • View Affiliations

  • Published online on: August 4, 2016     https://doi.org/10.3892/or.2016.5004
  • Pages: 2225-2235
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Abstract

The aim of the present study was to evaluate the promoter methylation status of SEPT9_v2 in breast cancer and to detect this methylated gene in circulating tumor DNA (ctDNA) in plasma. Bisulfite sequencing was performed with a next generation sequencer. Methylation of the SEPT9_v2 promoter was found in 67% (8/12) of breast cancer cell lines and 53% (10/19) of breast tumor tissue, but not in normal breast tissue (0/19). A clear inverse correlation was observed between the expression of SEPT9_v2 mRNA and the methylation index (MI) both in cell lines and breast cancer tissues. The MI of SEPT9_v2 was significantly higher in non-basal subtype of breast cancer (13.0%, n=84) than in basal subtype (3.0%, n=23) (P<0.0001). Methylated SEPT9_v2 ctDNA in plasma was detected in 11% (9/82) of primary breast cancer patients and 52% (26/50) of metastatic breast cancer patients, but not in the healthy controls (0/51). These results indicate that SEPT9_v2 promoter hypermethylation, which silences the expression of SEPT9_v2 mRNA, is observed in a significant proportion of breast tumors, and that methylated SEPT9_v2 may serve as a novel tumor marker for breast cancer.
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October-2016
Volume 36 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Matsui S, Kagara N, Mishima C, Naoi Y, Shimoda M, Shimomura A, Shimazu K, Kim SJ and Noguchi S: Methylation of the SEPT9_v2 promoter as a novel marker for the detection of circulating tumor DNA in breast cancer patients. Oncol Rep 36: 2225-2235, 2016
APA
Matsui, S., Kagara, N., Mishima, C., Naoi, Y., Shimoda, M., Shimomura, A. ... Noguchi, S. (2016). Methylation of the SEPT9_v2 promoter as a novel marker for the detection of circulating tumor DNA in breast cancer patients. Oncology Reports, 36, 2225-2235. https://doi.org/10.3892/or.2016.5004
MLA
Matsui, S., Kagara, N., Mishima, C., Naoi, Y., Shimoda, M., Shimomura, A., Shimazu, K., Kim, S. J., Noguchi, S."Methylation of the SEPT9_v2 promoter as a novel marker for the detection of circulating tumor DNA in breast cancer patients". Oncology Reports 36.4 (2016): 2225-2235.
Chicago
Matsui, S., Kagara, N., Mishima, C., Naoi, Y., Shimoda, M., Shimomura, A., Shimazu, K., Kim, S. J., Noguchi, S."Methylation of the SEPT9_v2 promoter as a novel marker for the detection of circulating tumor DNA in breast cancer patients". Oncology Reports 36, no. 4 (2016): 2225-2235. https://doi.org/10.3892/or.2016.5004