RT Journal Article
SR Electronic
T1 Aberrant promoter methylation of CDH13 and MGMT genes is associated with clinicopathological characteristics of primary non small cell lung carcinoma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P1224
VO 40
IS Suppl 56
A1 Milica Kontic
A1 Jelena Stojsic
A1 Dragana Jovanovic
A1 Simona Ognjanovic
A1 Heather Nelson
A1 Susan Puumala
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/P1224.abstract
AB Introduction: Systemic methylation changes may be a diagnostic marker for tumor development or prognosis. We investigate the relationship between gene methylation in lung tumors relative to normal lung tissue, and whether DNA methylation changes can be detected in paired blood samples.Material and methods: 65 patients were enrolled in a surgical case series of non-small cell lung cancer (NSCLC) at a single institution. Using bisulfite pyrosequencing, CpG methylation was quantified at five genes (RASSF1A, CDH13, MGMT, ESR1 and DAPK) in lung tumor, pathologically normal lung tissue, and circulating blood from enrolled cases.Results: The analyses of methylation in tumors compared to normal lung identified higher methylation of CDH13, RASSF1A and DAPK, while ESR1 and MGMT methylation did not differ significantly between these tissue types. We examined whether the three aberrantly methylated genes could be detected in blood. The difference in methylation observed in tumors was not reflected in methylation status of matching blood samples, indicating a low feasibility of detecting lung cancer by analyzing these genes in a blood-based test. Lastly we probed whether tumor methylation was associatied with clinical and demographic characteristics. Histology and gender were associated with methylation at the CDH13, while stage was associated with methylation at MGMT.Conclusion: Our results show higher methylation of RASSF1A, CDH13 and DAPK genes in lung tumors compared to normal lung. The lack of reflection of these methylation changes in blood samples from patients with NSCLC indicate their poorly suitability for a screening test.