Altered DNA Methylation of MAP3K6 and HPCAL1 as Potential Predictors for Persistent Trophoblastic Disease. Homo sapiens

Patients with molar pregnancy are at risk of developing persistent trophoblastic disease (PTD). Previous study indicated that PTD risk was not related to evacuation time of hydatidiform mole (HM), leading to our hypothesis that HM might be pre-programmed before evacuation to determine the PTD risk. Considering the similarity between PTD and tumorigenesis, we investigated the methylation alterations in PTD conceptus using reduced representation bisulfite sequencing (RRBS), in order to identify potential predictors for PTD. Overall design: 10 persistent trophoblastic disease (PTD) samples were chosen on the basis of the karyotype (46, XX), parental origin (P1P1) of the mole genome and the gestational age at evacuation between 9 and 12 weeks. 10 non-PTD samples were chosen upon the same criteria. Another 22 samples (10 PTD versus 12 non-PTD) were collected for validation experiment. Data on clinical features and chemotherapy were collected from gynecologic and oncologic hospital records. All patients had at least 6 months of follow-up from evacuation date, and the median follow-up time was 10.4 years. The regional Committee on Biomedical Research Ethics approved the study and all patients gave informed consent.