The Enigmatic Teratoma

Purpose: Mature cystic teratomas of the ovary can contain skin, hair, muscle, and bone and are usually found in women of reproductive age. Elucidating epigenomic aberrations in these teratomas may result in a better understanding of their stepwise developmental processes and molecular bases. Methods: Here, we analyzed the methylation statuses of promoter regions of 25 tumor suppressor genes, using a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA)–based approach, in 12 mature cystic teratomas of the ovary. Results: Methylated KLLN, RARB, CDKN2B, and GSTP1 and unmethylated MLH1 were specific to all 12 mature cystic teratomas of the ovary. Methylated genes with a high frequency among samples included APC and CD44, in addition to CDKN2A, MLH1, ATM, HIC1, and CDH13. Those with a moderate frequency included CASP8, ESR1, RASSF1, PTEN, KLLN, BRCA2, TP73, BRCA1, CDKN1B, RASSF1, CHFR, and TIMP3, and those with a low frequency included CADM1, FHIT, DAPK1, and VHL. Conclusions: Aberrant promoter methylations of GSTP1, RARB, ATM, CDKN2B, and KLLN were observed frequently in mature cystic teratomas of the ovary, which may explain, as suggested in the literature, processes such as osteogenesis (GSTP1, RARB, and ATM), adipocyte differentiation (RARB and ATM), myofibroblast differentiation (CDKN2B), and thyroid differentiation (KLLN). These DNA methylation markers may provide a better understanding of the specific developmental processes of mature cystic teratomas of the ovary.