Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Background: Hepatoblastoma, the most common pediatric liver malignancy, is cured by chemotherapy and surgical resection. Locally invasive/multifocal tumors require liver transplantation (LTx). A unique tumor biology comprising molecular and histological heterogeneity, largely defined in surgically resectable tumors, likely determines outcomes. Independent studies of tumors requiring LTx may identify distinct or consensus genetic drivers to improve treatment selection.
Methods: Paired end whole exome sequencing with Agilent SureSelect v reagents and Illumina HiSeq 2500 was performed on matched tumor and blood samples from 11 Caucasian children with LTx for hepatoblastoma. Somatic copy number (CN) variants were identified using Exome CNV and enriched genomic regions were computed using GISTIC.
Results: Mean age was 2.9±0.44 years, male: female distribution was 8:3. Nine children are alive and cancer-free including one after resection of post-LTx lung metastasis. Two children died from recurrent tumor. Among 10 of 11 patients with detectable changes, somatic CN gains were more prevalent, with a single enriched focal CN loss on chromosome (chr) 1q. Recurrent somatic CN gains at chr 1q, 2q, 12q, and 20q appeared consistent with reports from resectable tumors by others. Novel recurrent gains were observed at chr 3q, 5q, 6q, 10p, 11q, and 13q. The most prevalent somatic CN gain at 11q21, (q=0.002), harbors BIRC2 (cIAP1) and BIRC3 (cIAP2) genes, previously reported in liver cancer, and the family with sequence similarity 76, member B (FAM76B) gene, whose overexpression in lung cancer predicts poor survival. Somatic CN gains in the 20q13.33, (q=0.002) locus harboring the synaptonemal complex protein 2 (SYCP2) gene occured in three children with recurrence/metastasis. SYCP2 gene mutations associate with colon cancer and with FAM76B gene mutations in breast cancer. Other CN gains encompassed the oncogenes JMJD4 (1q42.13, q=0.015), DYNC1I2 (2q31.1, q=0.015), UFM1 (13q13.3, q=0.041) and ANKRD30A (10p11.21, q=0.045).
Conclusions: In this first report, unresectable hepatoblastoma requiring LTx shows molecular heterogeneity, with somatic amplifications in several loci that are shared with, or are distinct from those seen in resectable tumors. Somatic mutations in the SYCP2 gene locus in recurrent/metastatic tumors illustrates the added prognostic value of molecular risk-stratification.
CITATION INFORMATION: Ningappa M, Higgs B, Ranganathan S, Ashokkumar C, Sindhi R. The Heterogenous Genomic Landscape of Unresectable Hepatoblastoma Requiring Liver Transplantation: Prognostic Implications. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Ningappa M, Higgs B, Ranganathan S, Ashokkumar C, Sindhi R. The Heterogenous Genomic Landscape of Unresectable Hepatoblastoma Requiring Liver Transplantation: Prognostic Implications. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/the-heterogenous-genomic-landscape-of-unresectable-hepatoblastoma-requiring-liver-transplantation-prognostic-implications/. Accessed October 27, 2020.
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