Aberrant methylation of the HIC1 promoter is a frequent event in specific pediatric neoplasms

Purpose: To determine the role of methylation of HIC1 , a candidate tumor suppressor gene on 17p13.3, in various types of pediatric tumors. Experimental Design: We examined the methylation status of the HIC1 promoter by methylation specific PCR in 157 pediatric tumors and 27 nonmalignant tissues. We correlated methylation with mRNA expression by reverse transcription-PCR in eight tumor-derived cell lines. Results: HIC1 methylation was frequent in medulloblastomas (80%, 12 of 15), retinoblastomas (67%, 6 of 9), rhabdomyosarcomas (59%, 13 of 22), germ cell tumors (55%, 6 of 11), and neurouroblastic tumors (36%, 14 of 39); neuroblastomas (43%, 12 of 28); ganglioneuromas (17%, 1 of 6); and ganglioneuroblastomas (20%, 1 of 5). In contrast, a low incidence of methylation was observed in osteosarcomas (17%, 2 of 12), Ewing’s tumors (9%, 1 of 11), Wilms’ tumors (3%, 1 of 31), and hepatoblastomas (0%, 0 of 7). HIC1 methylation was more frequent in the aggressive alveolar subtype of rhabdomyosarcomas (100%, 8 of 8) than the embryonal subtype (33%, 4 of 12; P HIC1 mRNA. Expression was strongly induced in all cell lines by treatment with the demethylating agent 5-aza 2′deoxycytidine. Conclusions: Our data suggest that aberrant methylation of HIC1 may play a role in the pathogenesis of specific pediatric tumors.