Methylation profiling of mesothelioma using real-time methylation-specific PCR: A pilot study

We tested whether methylation profiles generated by real-time methylation-specific PCR (MSP) can be useful in differentiating benign, reactive mesothelial cell proliferation (RM) from malignant mesothelioma (MM). Forty-two of the 63 cases (67%) yielded informative results for RAR beta 2, GPC3, CDKN2A (p16), TERT, and CCND2 (cyclinD2) gene methylation. DNA methylation of any gene was observed in much higher frequency in MM cases than RM cases (63% vs. 33%, P < 0.05). Individual gene methylation was higher in the MM than the RM cases for most of the genes; however, this was not statistically significant (RAR beta 2: 58% vs. 33%, P > 0.05; GPC3: 36% vs. 27%, P > 0.05; CDKN2A: 4% vs. 0%; TERT: 4% vs. 0%), while CCND2 methylation was not detected in any case. Although preliminary, we demonstrate that real-time MSP can be applied to archival specimens and gene methylation profiling may have potential to be a useful ancillary tool to help distinguish MM front RM.