Identification of aberrant methylation regions in neuroblastoma by screening of tissue‐specific differentially methylated regions123. Issue 3 (21st August 2012)

• Record Type: Journal Article
• Authors: Sugito, Kiminobu; Kawashima, Hiroyuki; Uekusa, Shota; Yoshizawa, Shinsuke; Hoshi, Reina; Furuya, Takeshi; Kaneda, Hide; Hosoda, Toshifumi; Masuko, Takayuki; Ohashi, Kensuke; Ikeda, Taro; Koshinaga, Tsugumichi; Fujiwara, Kyoko; Igarashi, Jun; Ghosh, Srimoyee; Held, William A.; Nagase, Hiroki
• Is Part Of: Pediatric blood & cancer. Volume 60:Issue 3(2013:Mar.)
• Page Start: 383
• Page End: 389
• Publication Date: 2012-08-21
• Subjects: Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.24282
• Languages: English
• ISSNs: 1545-5009

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="abs1-1" sec-type="section"> <title>Background</title> <p>The identification of tissue‐specific differentially methylated regions (tDMRs) is key to our understanding of mammalian development. Research has indicated that tDMRs are aberrantly methylated in cancer and may affect the oncogenic process.</p> </sec> <sec id="abs1-2" sec-type="section"> <title>Procedure</title> <p>We used the MassARRAY EpiTYPER system to determine the quantitative methylation levels of seven neuroblastomas (NBs) and two control adrenal medullas at 12 conserved tDMRs. A second sample set of 19 NBs was also analyzed. Statistical analysis was carried out to determine the relationship of the quantitative methylation levels to other prognostic factors in these sample sets.</p> </sec> <sec id="abs1-3" sec-type="section"> <title>Results</title> <p>Screening of 12 tDMRs revealed 2 genomic regions (<italic>SLC16A5</italic> and <italic>ZNF206</italic>) with frequent aberrant methylation patterns in NB. The methylation levels of <italic>SLC16A5</italic> and <italic>ZNF206</italic> were low compared to the control adrenal medullas. The <italic>SLC16A5</italic> methylation level (cut‐off point, 13.25%) was associated with age at diagnosis, disease stage, and Shimada classification but not with <italic>MYCN</italic> amplification. The <italic>ZNF206</italic> methylation level (cut‐off point, 68.80%) was associated with all of the prognostic factors analyzed. Although the methylation levels at these regions did not reach statistical significance in their association with prognosis in mono‐variant analysis, patients with both hypomethylation of <italic>SLC16A5</italic> and hypermethylation of <italic>ZNF206</italic> had a significantly prolonged event‐free survival, when these two variables were analyzed together.</p> </sec> <sec id="abs1-4" sec-type="section"> <title>Conclusions</title> <p>We demonstrated that two tDMRs frequently displayed altered methylation patterns in the NB genome, suggesting their distinct involvement in NB development/differentiation. The combined analysis of these two regions could serve as a diagnostic biomarker for poor clinical outcome. Pediatr Blood Cancer 2013; 60: 383–389. © 2012 Wiley Periodicals, Inc.</p> </sec> </abstract>