title: M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity.
abstract: The mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) functions in the intracellular trafficking of lysosomal enzymes, the activation of the potent growth inhibitor, transforming growth factor beta 2, and the degradation of IGF2 (ref. 1), a mitogen often overproduced in tumours. We have recently shown that 70% of human hepatocellular tumours have loss of heterozygosity (LOH) at the M6P/IGF2R locus which maps to chromosome 6q26-q27 (ref. 8). Using a coarse screen, we have now identified point mutations in the remaining allele of 25% of human hepatocellular carcinomas (HCCs) with LOH. These mutations give rise to truncated receptor protein and significant amino acid substitutions, and provide evidence that the M6P/IGF2R gene functions as a tumour suppressor in human liver carcinogenesis.
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002417:Cattle; D004252:DNA Mutational Analysis; D005110:Extracellular Space / Q000737:chemistry; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D017354:Point Mutation; D051381:Rats; D017527:Receptor, IGF Type 2 / Q000032:analysis / Q000235:genetics*
chemical_list: D017527:Receptor, IGF Type 2