The genomic landscape of fibrolamellar hepatocellular carcinoma: Whole genome sequencing of ten patients Journal Article


Authors: Darcy, D. G.; Chiaroni-Clarke, R.; Murphy, J. M.; Honeyman, J. N.; Bhanot, U.; LaQuaglia, M. P.; Simon, S. M.
Article Title: The genomic landscape of fibrolamellar hepatocellular carcinoma: Whole genome sequencing of ten patients
Abstract: Fibrolamellar hepatocellular carcinoma is a rare, malignant liver tumor that often arises in the otherwise normal liver of adolescents and young adults. Previous studies have focused on biomarkers and comparisons to traditional hepatocellular carcinoma, and have yielded little data on the underlying pathophysiology. We performed whole genome sequencing on paired tumor and normal samples from 10 patients to identify recurrent mutations and structural variations that could predispose to oncogenesis. There are relatively few coding, somatic mutations in this cancer, putting it on the low end of the mutational spectrum. Aside from a previously described heterozygous deletion on chromosome 19 that encodes for a functional, chimeric protein, there were no other recurrent structural variations that contribute to the tumor genotype. The lack of a second-hit mutation in the genomic landscape of fibrolamellar hepatocellular carcinoma makes the DNAJB1-PRKACA fusion protein the best target for diagnostic and therapeutic advancements. The mutations, altered pathways and structural variants that characterized fibrolamellar hepatocellular carcinoma were distinct from those in hepatocellular carcinoma, further defining it as a distinct carcinoma.
Keywords: adolescent; adult; clinical article; controlled study; human tissue; middle aged; young adult; gene mutation; sequence analysis; single nucleotide polymorphism; somatic mutation; hepatocellular carcinoma; chromosome 19; genotype; liver cancer; genome; mutation rate; chromosome deletion; sequencing; indel mutation; liver carcinogenesis; fibrolamellar; cancer; human; male; female; article; whole genome sequencing; fibrolamellar hepatocellular carcinoma
Journal Title: Oncotarget
Volume: 6
Issue: 2
ISSN: 1949-2553
Publisher: Impact Journals  
Date Published: 2015-01-01
Start Page: 755
End Page: 770
Language: English
PROVIDER: scopus
PUBMED: 25605237
PMCID: PMC4359253
DOI/URL:
Notes: Export Date: 2 March 2015 -- Source: Scopus
Citation Impact
MSK Authors
  1. Umeshkumar Kapaldev Bhanot
    42 Bhanot
  2. Jennifer Michelle Murphy
    11 Murphy
  3. David Gene Darcy
    6 Darcy