Back to Journals » OncoTargets and Therapy » Volume 7

Elevation of methylated DNA in KILLIN/PTEN in the plasma of patients with thyroid and/or breast cancer

Authors Ng E, Shin V, Leung C, Chan V, Law F, Siu M, Lang B, Ma E, Kwong A

Received 26 August 2013

Accepted for publication 16 December 2013

Published 11 November 2014 Volume 2014:7 Pages 2085—2092

DOI https://doi.org/10.2147/OTT.S53597

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3


Enders K Ng,1 Vivian Y Shin,1 Candy P Leung,1 Vivian W Chan,2 Fian B Law,2,3 Man T Siu,1 Brian H Lang,1 Edmond S Ma,2,3 Ava Kwong1,3

1Department of Surgery, The University of Hong Kong, 2Department of Molecular Pathology and Department of Surgery, Hong Kong Sanatorium and Hospital, 3Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong

Abstract: Around 80% of mutations in the PTEN gene have been reported to be associated with diseases such as Cowden syndrome, which is an autosomal dominant disorder associated with an increased risk of developing breast, thyroid, and endometrial neoplasms. Recent studies have also demonstrated that KILLIN, which is located proximally to PTEN, shares the same transcription start site, and is assumed to be regulated by the same promoter, but is transcribed in the opposite direction. In this regard, we postulate that there may be a connection between KILLIN/PTEN genes and breast and thyroid cancers. Using real-time quantitative polymerase chain reaction (qPCR), we found that expression of KILLIN, but not PTEN, was significantly decreased in 23 Chinese women with a personal history of breast and thyroid cancer or a personal history of breast cancer and a family history of thyroid cancer, or vice versa, and at least two persons in the family with thyroid cancer or at a young age <40 years, when compared with healthy controls (P<0.0001). No PTEN mutations were found in these 23 patients. We then developed a simple methylation-sensitive restriction enzyme digestion followed by real-time quantitative assay to quantify plasma methylated KILLIN/PTEN DNA in these patients. Plasma levels of methylated KILLIN/PTEN DNA were significantly increased in these patients when compared with healthy controls (P<0.05). This study shows that plasma methylated KILLIN/PTEN DNA was significantly elevated, suggesting hypermethylation of the KILLIN/PTEN promoter in breast and thyroid cancer patients.

Keywords: KILLIN, PTEN, hypermethylation, breast cancer, thyroid cancer

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]