title: Comparative genomic hybridization analysis of hepatoblastoma reveals high frequency of X-chromosome gains and similarities between epithelial and stromal components.
abstract: Hepatoblastoma (HB) is the most common liver tumor in childhood and differs in its environmental risk factors and genetic background from hepatocellular carcinoma. HB is associated with inherited conditions such as familial adenomatous polyposis and Beckwith-Wiedemann syndrome, suggesting the importance of genetic abnormalities in the pathogenesis and progression of this disease. It has a very polymorphous morphology. A diverse range of cytogenetic alterations has been reported to date, the most frequent being trisomy 2 and trisomy 20. Thirty-five HB specimens from 31 patients (22 purely epithelial, 4 purely mesenchymal, 9 mixed) were examined by comparative genomic hybridization (CGH), a technique that enables us to screen the entire tumor genome for genetic losses and gains. Our aims were as follows: (1) to characterize chromosome abnormalities that appear in this tumor and (2) to identify possible differences between different histologic subtypes of HB. We found significant gains of genetic material, with very little difference in the number and type of alterations between the different histologic components of HB. The most frequent alterations were gains of Xp (15 cases, 43%) and Xq (21 cases, 60%). This finding was also confirmed by fluorescent in situ hybridization performed on nuclei extracted from 6 specimens. Other common alterations were 1p-, 2q+, 2q-, 4q-, and 4q+. We found no difference between different histologic subtypes, a finding that may be in agreement with the hypothesis of a common clonal origin for the different components. An hitherto-unreported high frequency of X chromosome gains may support the assumption that X-linked genes are involved in the development of this neoplasm.
authors.affiliation: Institute of Pathology, University of Basel, Switzerland.
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Terracciano
authors.forename: Barbara
authors.initials: B
authors.lastname: Bernasconi
authors.forename: Peter
authors.initials: P
authors.lastname: Ruck
authors.forename: Thomas
authors.initials: T
authors.lastname: Stallmach
authors.forename: Jakob
authors.initials: J
authors.lastname: Briner
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.forename: Raffaella
authors.initials: R
authors.lastname: Vecchione
authors.forename: Lucio
authors.initials: L
authors.lastname: Pollice
authors.forename: Guido
authors.initials: G
authors.lastname: Pettinato
authors.forename: Barbara
authors.initials: B
authors.lastname: Gürtl
authors.forename: Manfred
authors.initials: M
authors.lastname: Ratschek
authors.forename: Ronald
authors.initials: R
authors.lastname: De Krijger
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bruder
mesh_terms: D002467:Cell Nucleus / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D041321:Chromosomes, Human, X; D004273:DNA, Neoplasm / Q000235:genetics*; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D018197:Hepatoblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009693:Nucleic Acid Hybridization; D017154:Stromal Cells / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm