title: Quantitative detection ofTUSC3promoter methylation -a potential biomarker for prognosis in lung cancer.
abstract: Aberrant promoter methylation of tumor relevant genes frequently occurs in early steps of carcinogenesis and during tumor progression. Epigenetic alterations could be used as potential biomarkers for early detection and for prediction of prognosis and therapy response in lung cancer. The present study quantitatively analyzed the methylation status of known and potential gatekeeper and tumor suppressor genes [O-6-methylguanine-DNA methyltransferase (MGMT), Ras association domain family member 1A (RASSF1A), Ras protein activator like 1 (RASAL1), programmed cell death 4 (PDCD4), metastasis suppressor 1 (MTSS1) and tumor suppressor candidate 3 (TUSC3)] in 42 lung cancers and in corresponding non-malignant bronchus and lung tissue using bisulfite-conversion independent methylation-quantification of endonuclease-resistant DNA (MethyQESD). Methylation status was associated with clinical and pathological parameters. No methylation was found in the promoter regions ofPDCD4andMTSS1of either compartment.MGMT,RASSF1AandRASAL1showed sporadic (up to 26.2%) promoter methylation. The promoter ofTUSC3, however, was frequently methylated in the tumor (59.5%), benign bronchus (67.9%) and alveolar lung (31.0%) tissues from each tumor patient. The methylation status ofTUSC3was significantly associated with smaller tumor size (P=0.008) and a longer overall survival (P=0.013). Pooled blood DNA of healthy individuals did not show any methylation of either gene. Therefore, methylation ofTUSC3shows prognostic and pathobiological relevance in lung cancer. Furthermore, quantitative detection ofTUSC3promoter methylation appears to be a promising tool for early detection and prediction of prognosis in lung cancer. However, additional studies are required to confirm this finding.
authors.affiliation: Institute of Pathology, University of Regensburg, D-93053 Regensburg, Bavaria, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Duppel
authors.affiliation: Department of Pathology, Caritas-Hospital, D-97980 Bad Mergentheim, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Woenckhaus
authors.affiliation: Department of Internal Medicine II, University Hospital Regensburg, D-93053 Regensburg, Bavaria, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schulz
authors.affiliation: Department of Thoracic Surgery, University Hospital Regensburg, D-93053 Regensburg, Bavaria, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Merk
authors.affiliation: Institute of Pathology, University of Regensburg, D-93053 Regensburg, Bavaria, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dietmaier
keywords: lung cancer; prognosis; quantitative methylation analysis; survival; tumor suppressor candidate 3