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

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). We investigated the methylation status of CTNNA1 promoter using methylation-specific PCR (MSP) and analyzed its clinical significance in Chinese MDS patients. 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). Our data confirm that aberrant CTNNA1 methylation is a common event and is associated with higher IPSS risk in MDS.

Citation

Jun Qian, Xing-Xing Chen, Wei Qian, Jing Yang, Xiang-Mei Wen, Ji-Chun Ma, Zhao-Qun Deng, Zhen Qian, Ying-Ying Zhang, Jiang Lin. Aberrant hypermethylation of CTNNA1 gene is associated with higher IPSS risk in patients with myelodysplastic syndrome. Clinical chemistry and laboratory medicine : CCLM / FESCC. 2014 Dec;52(12):1859-65

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PMID: 25153418

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