DNA methylation profile of 28 potential marker loci in malignant mesothelioma.
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.
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.
Jeffrey A
JA
Tsou
Janice S
JS
Galler
Anil
A
Wali
Wei
W
Ye
Kimberly D
KD
Siegmund
Susan
S
Groshen
Peter W
PW
Laird
Sally
S
Turla
Michael N
MN
Koss
Harvey I
HI
Pass
Ite A
IA
Laird-Offringa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016000:Cluster Analysis; D019175:DNA Methylation; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008654:Mesothelioma / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins