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Aberrant methylation of protocadherin 17 and its prognostic value in pediatric acute lymphoblastic leukemia
Author(s) -
Uyen Thanh Nha,
Sakashita Kazuo,
AlKzayer Lika'a Fasih Y.,
Nakazawa Yozo,
Kurata Takashi,
Koike Kenichi
Publication year - 2017
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.26259
Subject(s) - methylation , dna methylation , protocadherin , cdh1 , medicine , biomarker , bisulfite sequencing , cancer research , oncology , gene , microbiology and biotechnology , biology , genetics , cadherin , gene expression , cell
Abstract Background The outcome of approximately 20% of patients with acute lymphoblastic leukemia (ALL) remains poor because of disease recurrence. We examined whether DNA methylation of cadherin superfamily genes is a useful biomarker for ALL relapse. Procedure We used Infinium Methylation 450K Arrays to assess genome‐wide DNA methylation status. The methylation status of each individual gene was then determined by a combination of bisulfite restriction analysis and genome bisulfite sequencing. mRNA expression was evaluated by reverse‐transcriptase PCR (RT‐PCR) and quantitative real‐time PCR. Results Cadherin superfamily genes including cadherin (CDH) 1 , protocadherin (PCDH) 8 , and PCDH17 were selected for analysis of methylation status. In 40 patient samples with B‐cell precursor (BCP) ALL at diagnosis, the methylation frequencies of CDH1 , PCDH8 , and PCDH17 were 62.5, 55, and 30%, respectively. CDH1 and PCDH8 methylation was also detected in 80 and 20% of control bone marrow (BM) samples, respectively. On the contrary, PCDH17 was unmethylated in all control BM samples. There was a significant correlation between the methylation status of PCDH17 (but not CDH1 and PCDH8 ) and event‐free survival or overall survival. Univariate and multivariate analyses showed that only PCDH17 methylation was associated with an increased risk for relapse and mortality in patients with BCP ALL. Conclusion PCDH17 methylation at diagnosis was closely related to poor prognosis and thus could be used as a new biomarker to predict relapse in patients with BCP ALL.