Klin Padiatr 2014; 226 - A24
DOI: 10.1055/s-0034-1374845

Identification of genetic alterations in pediatric hepatocellular carcinomas

A Carmichael 1, T Pietsch 2, C Vokuhl 1, I Leuschner 1
  • 1Kiel Paediatric Tumor Registry, Dept. of Pediatric Pathology, Kiel University, Kiel
  • 2Dept. of Neuropathology, Bonn University, Bonn, Germany

Paediatric hepatocellular carcinomas (pHCC) are rare neoplasms. Due to a worse prognosis of pHCC and different treatment approaches in comparison to the hepatoblastoma (HBL), an exact differentiation is required.

Building on a previously published study by Weber et al., (AJP, 2000) which looked at HBL genomic alterations, we aim to compare the two cohorts and to identify characteristic chromo-somal alterations of pHCC.

Genomic DNA was extracted from 34 pHCC, including 4 cases of the fibrolamellar subtype and 3 cases with partial fibrolamellar differentiation. By using molecular inversion profiling a Genome-wide copy analysis was performed.

Most frequent alterations were gains of chromosome 1q (65%), 2q (35%), 6 p (35%), 20 (35%), 19q (32%), 8q (29%) and losses of 1 p (56%) and 4q (38%). Furthermore, GISTIC analysis identified focal alterations including losses of the AXIN1 locus on 16p13.3 in 53% of cases. 6/34 pHCC lacked larger chromosomal imbalances. Of note, 5 of these 6 genomically stable tumours showed fibrolamellar differentiation. When comparing pHCC to HBL, losses of 1 p (56% vs. 3%), and gains of 6 p (35% vs. 3%) and 19q (32% vs. 0%) were significantly more frequent in pHCC.

For the first time, we are able to identify characteristic alterations of pHCC. These may indicate a specific pathogenesis of these neoplasms, thereby differentiating these tumours from HBL.