A study of 42 cases of positive SHOX2 and PTGER4 methylation combined with elevated serum CYFRA 21-1 demonstrated an impressive sensitivity (91.3%) and specificity (97.6%) in differentiating mesothelioma from reactive mesothelial hyperplasia; however, this diagnostic biomarker signature needs to be validated in a large prospective trial [15]. The gene discussed is PTGER4; the disease is mesothelioma.