Authors: MarieLuise Buchholtz Ansgar Brüning Ioannis Mylonas Julia Jückstock
Publish Date: 2014/02/21
Volume: 290, Issue: 1, Pages: 149-154
Abstract
Due to very unspecific symptoms ovarian cancer often is diagnosed only at a late stage of the disease Thus morbidity and mortality of the patients are high Even the established tumor marker CA125 shows only low specificity rising the need for alternative biomarkers capable of detecting early stages of ovarian cancer We analyzed the expression of the tumor suppressor candidate gene LDOC1 leucine zipper downregulated in cancer 1 as a potential early biomarker in ovarian cancer cell linesA total of seven ovarian cancer cell lines were analyzed by RTPCR reverse transcriptase polymerase chain reaction and realtime PCR for expression of LDOC1 Verification of promoter methylation was performed using methylationspecific primers on bisulfitemodified genomic DNAThree out of seven ovarian cancer cell lines showed a complete loss of LDOC1 gene expression LDOC1 silencing was caused neither by gene deletion nor gene rearrangements but by methylation and subsequent inactivation of the concerned promoter as proofed by methylation specific primers Similarly promoter methylation could be inhibited by adding AdC 5aza2′deoxycytidine an inhibitor of DNA methyltransferases As a result a reactivation of the LDOC1 gene was seenThe tumor suppressor gene LDOC1 in ovarian cancer cell lines is downregulated by promoter methylation and thus may serve as an early biomarker Further investigation will show if detection of methylated LDOC1 in peripheral blood has both adequate sensitivity and specificity for a timely noninvasive detection of ovarian cancer
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