Somatic mutations in the kinase domain of the MET/hepatocyte growth factorreceptor gene in childhood hepatocellular carcinomas

The MET protooncogene encodes a transmembrane tyrosine kinase identified as the receptor of a polypeptide known as hepatocyte growth factor/scatter fa ctor. We performed PCR-based single-strand conformational polymorphism and sequencing analysis of the tyrosine kinase domain of the MET gene (exon 15- 19) in 75 primary liver cancers. Three missense mutations were detected exc lusively in 10 childhood hepatocellular carcinomas (HCCs), while no mutatio ns were detected in 16 adult HCCs, 21 cholangiocarcinomas, or 28 hepatoblas tomas. The extremely short incubation period from hepatitis B virus infecti on to the genesis of childhood HCC as compared with the adult HCC suggests that there may be an additional mechanism that accelerates the carcinogenes is of childhood HCC. Our results indicate that mutations of the tyrosine ki nase domain of the MET gene may be involved in the acceleration of the carc inogenesis in childhood HCC.