期刊
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
卷 164, 期 4, 页码 993-997出版社
WILEY
DOI: 10.1002/ajmg.a.36364
关键词
hepatoblastoma; Simpson-Golabi-Behmel syndrome; CTNNB1; GPC3
资金
- Ministry of Health, Labour and Welfare, Japan the Health and Labour Sciences Research Grant for Research on rare and intractable diseases [Jitsuyoka(Nanbyo)-Ippan-003, Jitsuyoka(Nanbyo)-Ippan-013]
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 -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. (c) 2014 Wiley Periodicals, Inc.
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