Abstract
The mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) functions in the intracellular trafficking of lysosomal enzymes1, the activation of the potent growth inhibitor, transforming growth factor β2, and the degradation of IGF2 (ref. 1), a mitogen often overproduced in tumours3–6. We have recently shown that 70% of human hepatocellular tumours have loss of heterozygosity (LOH) at the M6P/IGF2R locus7 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.
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De Souza, A., Hankins, G., Washington, M. et al. M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity. Nat Genet 11, 447–449 (1995). https://doi.org/10.1038/ng1295-447
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DOI: https://doi.org/10.1038/ng1295-447
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