PMID- 17659810 OWN - NLM STAT- MEDLINE DCOM- 20080111 LR - 20220408 IS - 0169-5002 (Print) IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 58 IP - 2 DP - 2007 Nov TI - DNA methylation profile of 28 potential marker loci in malignant mesothelioma. PG - 220-30 AB - Patients with malignant mesothelioma (MM), an aggressive cancer associated with asbestos exposure, usually present clinically with advanced disease and this greatly reduces the likelihood of curative treatment. MM is difficult to diagnose without invasive techniques; the development of non-invasively detectable molecular markers would therefore be highly beneficial. DNA methylation changes in cancer cells provide powerful markers that are potentially detectable non-invasively in DNA shed into bodily fluids. Here we examined the methylation status of 28 loci in 52 MM tumors to investigate their potential as molecular markers for MM. To exclude candidate MM markers that might be positive in biopsies/pleural fluid due to contaminating surrounding non-tumor lung tissue/DNA, we also examined the methylation of these markers in lung samples (age- or environmentally induced hypermethylation is frequently observed in non-cancerous lung). Statistically significantly increased methylation in MM versus non-tumor lung samples was found for estrogen receptor 1 (ESR1; p = 0.0002), solute carrier family 6 member 20 (SLC6A20; p = 0.0022) and spleen tyrosine kinase (SYK; p=0.0003). Examination of associations between methylation levels of the 28 loci and clinical parameters suggest associations of the methylation status of metallothionein genes with gender, histology, asbestos exposure, and lymph node involvement, and the methylation status of leucine zipper tumor suppressor 1 (LZTS1) and SLC6A20 with survival. FAU - Tsou, Jeffrey A AU - Tsou JA AD - Norris Cancer Center and Department of Surgery, Keck School of Medicine, University of Southern California, Room NOR6420, 1441 Eastlake Avenue, Los Angeles, CA 90089-9176, USA. FAU - Galler, Janice S AU - Galler JS FAU - Wali, Anil AU - Wali A FAU - Ye, Wei AU - Ye W FAU - Siegmund, Kimberly D AU - Siegmund KD FAU - Groshen, Susan AU - Groshen S FAU - Laird, Peter W AU - Laird PW FAU - Turla, Sally AU - Turla S FAU - Koss, Michael N AU - Koss MN FAU - Pass, Harvey I AU - Pass HI FAU - Laird-Offringa, Ite A AU - Laird-Offringa IA LA - eng GR - P30 CA014089/CA/NCI NIH HHS/United States GR - P30 CA014089-349012/CA/NCI NIH HHS/United States GR - P30 CA 14089/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20070730 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Biomarkers, Tumor) RN - 0 (Neoplasm Proteins) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*genetics MH - Cluster Analysis MH - *DNA Methylation MH - Female MH - Humans MH - Kaplan-Meier Estimate MH - Male MH - Mesothelioma/*genetics MH - Middle Aged MH - Neoplasm Proteins/genetics PMC - PMC2752414 MID - NIHMS33001 COIS- Conflict of interest statement I.A.L.-O. and P.W.L. are shareholders of Epigenomics AG, which has a commercial interest in the development of DNA markers for disease detection and diagnosis. None of the work performed in the laboratories of any of the authors is or has been supported by Epigenomics. EDAT- 2007/07/31 09:00 MHDA- 2008/01/12 09:00 PMCR- 2009/09/25 CRDT- 2007/07/31 09:00 PHST- 2007/02/07 00:00 [received] PHST- 2007/05/28 00:00 [revised] PHST- 2007/06/19 00:00 [accepted] PHST- 2007/07/31 09:00 [pubmed] PHST- 2008/01/12 09:00 [medline] PHST- 2007/07/31 09:00 [entrez] PHST- 2009/09/25 00:00 [pmc-release] AID - S0169-5002(07)00340-6 [pii] AID - 10.1016/j.lungcan.2007.06.015 [doi] PST - ppublish SO - Lung Cancer. 2007 Nov;58(2):220-30. doi: 10.1016/j.lungcan.2007.06.015. Epub 2007 Jul 30.