Abstract LB-205: Genome-wide copy number analysis of pediatric hepatocellular carcinomas: Identification of characteristic aberrations

Abstract

Abstract Hepatocellular carcinomas (HCC) of childhood are rare neoplams. Their pathogenesis is believed to be different from HCC in adulthood. The differential diagnosis from hepatoblastoma (HBL)is important because of worse prognosis of pediatric HCC (pHCC) and different treatment approaches. However, the diagnosis by conventional histological analysis may be difficult in some cases. Informations on chromosomal alterations in pHCC are lacking. The aim of this study was to identify recurrent chromosomal aberrations in a larger cohort of pHCC and compare it to a previously published cohort of HBL (Weber et al., American Journal of Pathology, 2000) to identify characteristic chromosomal alterations of pHCC. Genomic DNA was extracted from FFPE samples of a cohort of 34 pHCC including 4 cases of the fibrolamellar subtype and 3 cases with partial fibrolamellar differentiation from the archives of the German Pediatric Tumor Registry, University of Kiel. Genome-wide copy analysis was performed by molecular inversion profiling. GISTIC analysis was done to identify significant large and focal aberrations. Most frequent copy number alterations were gains of chromosome 1q (65%), 2q (35%), 6p (35%), 20 (35%), 19q (32%) and 8q (29%) and losses of chromosomal regions 1p (56%) and 4q (38%). In addition, GISTIC analysis identified several significant fokal alterations including losses of the AXIN1 tumor suppressor locus on 15q26 in 53% of cases. 6/34 pHCC lacked any larger chromosomal imbalances. Of note, 5 of these 6 genomically stable tumors showed fibrolamellar differentiation. When pHCC with fibrolamellar differentiation were compared to the other pHCC, loss of 1p and 4q and gains of 1q, 2q, 6q and 20 occurred significantly more frequent in the latter. When pHCC were compared to HBL, both entities shared similar alterations including gains if 1q and 2q, but losses of 1p (56% vs. 3%), and gains of 6p (35% vs. 3%) and 19q (32% vs. 0%) were significantly more frequent in pHCC. In this genome-wide copy number analysis of a large cohort of pHCC we were able to identify for the first time characteristic alterations which may indicate a specific pathogenesis of these neoplasms, may help to subclassify pHCC and to differentiate these tumors from HBL. Supported by the German Childhood Cancer Foundation. Citation Format: Torsten Pietsch, A. Carmichael, Christian Vokuhl, Ivo Leuschner. Genome-wide copy number analysis of pediatric hepatocellular carcinomas: Identification of characteristic aberrations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-205. doi:10.1158/1538-7445.AM2014-LB-205