Genomic Analysis of Hepatocellular Carcinoma

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a very rare and distinct subtype of hepatocellular carcinoma that occurs in the previously healthy livers of adolescents and young adults. The low incidence rate has kept FL-HCC an understudied cancer, thus the list of FL-HCC markers is limited and the genetic alterations driving its growth have remained unknown. In order to gain a better understanding of the molecular mechanisms underlying FL-HCC initiation and progression, we performed an in-depth genomic analyses of one tumor followed by immunohistochemistry validation on seven other tumors. We showed the expression of neuroendocrine markers in FL-HCC. In addition, DNA/RNA sequencing revealed that common cancer pathways are not visibly altered in FL-HCC but identified two novel structural variants, both resulting in fusion transcripts. Through in vitro studies, we demonstrated the oncogenic properties of these fusion transcripts. These experiments further highlight the tumorigenic role of gene fusions in the etiology of pediatric solid tumors and identify both candidate biomarkers and possible therapeutic targets for this lethal pediatric disease.]]>
Cases were identified from Stanford University Hospital and Lucille Packard Children's Hospital. Inclusion Criteria: Age 45 or younger Diagnosis of Fibrolamellar Hepatocellular Carcinoma, confirmed by histological analysis by a secondary Pathologist Enough FFPE or frozen tissue of both tumor and normal for immunohistochemical analysis Exclusion Criteria: Patients with hepatitis, increased background parenchymal fibrosis or tumor morphology atypical of FL-HCC ]]>
Study was conceptualized in 2011. IRB approval was obtained and specimens were collected and sequenced from Stanford University Hospital and Lucille Packard Children's Hospital in 2011-2012. The bulk of sequencing data analysis and experiments were performed in 2012-2013. Results were published in 2014. ]]>