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Vital factors in liver cancer

M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity De Souza AT, Hankins GR, Washington MK, Orton TC and Jirtle RL. Nature Genetics 1995; 11: 447-449

Department of Molecular Biology BIBRA International Carshalton, Surrey, SM5 4DS, UK

The mannose 6-phosphate/insulin-like growth fac tor-II receptor (M6P/IGF2R) functions in the in tracellular trafficking of lysosomal enzymes, the activation to the potent growth inhibitor, transform ing growth factor β, and the degradation of IGF2, 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 6q26-27. 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 substitu tions, and provide evidence that the M6P/IGF2R gene functions as a tumour suppressor in human liver carcinogenesis.

Human & Experimental Toxicology, Vol. 15, No. 6, 539-540 (1996)
DOI: 10.1177/096032719601500613


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