Abstract 5336: Methylation patterns in hepatoblastoma: A report from the Children's Oncology Group

Abstract

Abstract Introduction. Hepatoblastoma (HB) accounts for over 80% of all liver cancer diagnosed in children under 15 years of age in the United States. Aberrant DNA methylation has been implicated in the pathogenesis of multiple types of cancer, including HB. Global hypomethylation and DNA methylation in the promoter region of selected tumor suppressor genes, including RASSF1A, p16, SOCS1, CASP8, and MT1G, has been observed in previous studies of HB. Methods. A total of 47 flash-frozen samples of HB tumors were available for analysis. These tumors include 26 tumors from cases enrolled in Children's Oncology Group study AEPI04C1 (the HOPE study) and 21 tumors obtained as part of the Children's Oncology Group P9346 HB biology protocol. The Cooperative Human Tissue Network Pediatric Division (CHTN; Columbus, OH) provided 23 normal liver tissue samples from children ages 0—6 to serve as controls in this analysis. Initial multi-dimensional scaling (MDS) plots showed that 8 samples, 2 control and 6 patients, did not cluster with the other samples of the same group and were considered outliers. These 8 samples were removed from the study leaving a total of 62 samples, 21 control and 41 patients, remaining. Differentially methylated regions (DMR) were identified between control and patient samples using the bumphunter algorithm included in the minfi package. We used Ingenuity Pathway Analysis (IPA) to identify pathways that were enriched in the group of CpG with a change in methylation beta value of ≥39% between patients and controls. Results. We found 4833 DMR, which are associated with 3543 genes, when comparing HB patients and controls. Pathway analysis revealed 76 pathways enriched among the DMR. Conclusions. Identification of methylation patterns may elucidate the developmental stage at which HB arose and the at-risk period when environmental exposures could be most harmful. Further, understanding the relevant genetic pathways could lead to the development of new targets for therapy. Citation Format: Erin Marcotte, Logan G. Spector, Heather Nelson, Gail Tomlinson, Mark Krailo, Lauren Mills, Jenny Poynter. Methylation patterns in hepatoblastoma: A report from the Children's Oncology Group [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5336.