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Licensed Unlicensed Requires Authentication Published by De Gruyter August 12, 2014

Aberrant hypermethylation of CTNNA1 gene is associated with higher IPSS risk in patients with myelodysplastic syndrome

  • Jun Qian , Xing-xing Chen , Wei Qian EMAIL logo , Jing Yang , Xiang-mei Wen , Ji-chun Ma , Zhao-qun Deng , Zhen Qian , Ying-ying Zhang and Jiang Lin EMAIL logo

Abstract

Background:CTNNA1 gene is a putative tumor suppressor for its roles in inhibiting proliferation and promoting apoptosis. Aberrant expression of CTNNA1 is regulated by epigenetic mechanisms including both promoter methylation and histone deacetylation in hematopoietic malignancies. However, the clinical relevance of CTNNA1 methylation remains rarely known in myelodysplastic syndrome (MDS).

Methods: We investigated the methylation status of CTNNA1 promoter using methylation-specific PCR (MSP) and analyzed its clinical significance in Chinese MDS patients.

Results: Aberrant hypermethylation of CTNNA1 gene was identified in 22% (18/83) of the patients. CTNNA1 expression was significantly correlated with promoter methylation status (p<0.05). No significant differences were observed in the age, sex, and blood parameters between patients with and without CTNNA1 hypermethylation (p>0.05). The frequency of CTNNA1 hypermethylation was significantly higher in patients with isolated del(5q) (3/4, 75%) than those with other abnormal karyotypes (4/23, 17%) and also than those with normal karyotypes (11/54, 20%) (p=0.042 and 0.040, respectively). The patients with higher IPSS risks (Int-2/High) had significantly increased incidence of CTNNA1 methylation than those with lower risks (Low/Int-1) (36% vs. 15%, p=0.049). Although the estimated 50% survival time of the CTNNA1-methylated group [median 13 months, 95% confidence interval (CI) 3–22 months] was shorter than that of CTNNA1-unmethylated group (median 24 months, 95% CI 7–41 months), the difference was not statistically significant (p=0.330).

Conclusions: Our data confirm that aberrant CTNNA1 methylation is a common event and is associated with higher IPSS risk in MDS.


Corresponding authors: Jiang Lin, Laboratory Center, Affiliated People’s Hospital of Jiangsu University, 8 Dianli Road, 212002 Zhenjiang, P.R. China, Phone: +86 511 88915586, Fax: +86 511 85234387, E-mail: ; and Wei Qian, Laboratory Center, Affiliated People’s Hospital of Jiangsu University, 8 Dianli Road, 212002 Zhenjiang, P.R. China, Phone: +86 511 88917833, Fax: +86 511 85234387, E-mail:

Acknowledgments

This study was supported by National Natural Science Foundation of China (81270630, 81172592), Science and Technology Special Project in Clinical Medicine of Jiangsu Province (BL2012056), 333 Project of Jiangsu Province (BRA2011085, BRA2013136), Science and Technology Infrastructure Program of Zhenjiang (SS2012003), Social Development Foundation of Zhenjiang (SH2013042, SH2013082), the Innovation Project of Graduate Student in Jiangsu Province’s Ordinary University (CXLX12_0673), and Jiangsu Government Scholarship for Overseas Studies.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

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Received: 2014-4-24
Accepted: 2014-6-16
Published Online: 2014-8-12
Published in Print: 2014-12-1

©2014 by De Gruyter

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