Somatic CTNNB1 mutation in hepatoblastoma from a patient with Simpson-Golabi-Behmel syndrome and germline GPC3 mutation

Rika Kosaki, Toshiki Takenouchi, Noriko Takeda, Masayo Kagami, Kazuhiko Nakabayashi, Kenichiro Hata, Kenjiro Kosaki

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Simpson-Golabi-Behmel syndrome is a rare overgrowth syndrome caused by the GPC3 mutation at Xq26 and is clinically characterized by multiple congenital abnormalities, intellectual disability, pre/postnatal overgrowth, distinctive craniofacial features, macrocephaly, and organomegaly. Although this syndrome is known to be associated with a risk for embryonal tumors, similar to other overgrowth syndromes, the pathogenetic basis of this mode of tumorigenesis remains largely unknown. Here, we report a boy with Simpson-Golabi-Behmel syndrome who had a germline loss-of function mutation in GPC3. At 9 months of age, he developed hepatoblastoma. A comparison of exome analysis results for the germline genome and for the tumor genome revealed a somatic mutation, p.Ile35Ser, within the degradation targeting box of β-catenin. The same somatic mutation in CTNNB1 has been repeatedly reported in hepatoblastoma and other cancers. This finding suggested that the CTNNB1 mutation in the tumor tissue represents a driver mutation and that both the GPC3 and the CTNNB1 mutations contributed to tumorigenesis in a clearly defined sequential manner in the propositus. The current observation of a somatic CTNNB1 mutation in a hepatoblastoma from a patient with a germline GPC3 mutation supports the notion that the mutation in GPC3 may influence one of the initial steps in tumorigenesis and the progression to hepatoblastoma.

Original languageEnglish
Pages (from-to)993-997
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Issue number4
Publication statusPublished - 2014 Apr


  • CTNNB1
  • GPC3
  • Hepatoblastoma
  • Simpson-Golabi-Behmel syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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