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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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS THE IMPLICATIONS OF _IDH_ MUTATIONS FOR CANCER DEVELOPMENT AND

THERAPY Article 15 June 2021 LOSS OF _TP53_ COOPERATES WITH C-MET OVEREXPRESSION TO DRIVE HEPATOCARCINOGENESIS Article Open access 27 July 2023 IRON METABOLISM IN A MOUSE MODEL OF

HEPATOCELLULAR CARCINOMA Article Open access 16 January 2025 REFERENCES * Kornfeld, S. Structure and function of the mannose 6-phosphate/insulin-like growth factor II receptors. _A. Rev.

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1473–1478 (1994). Article  CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Safety of Medicines, Zeneca Pharmaceuticals, Alderley Park,

Macclesfield, Cheshire, SK10 4TG, UK Angus T. De Souza & Terry C. Orton * Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, 27710, USA Gerald R.

Hankins & Randy L. Jirtle * Department of Pathology, Duke University Medical Center, Durham, North Carolina, 27710, USA Mary K. Washington Authors * Angus T. De Souza View author

publications You can also search for this author inPubMed Google Scholar * Gerald R. Hankins View author publications You can also search for this author inPubMed Google Scholar * Mary K.

Washington View author publications You can also search for this author inPubMed Google Scholar * Terry C. Orton View author publications You can also search for this author inPubMed Google

Scholar * Randy L. Jirtle View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS

ARTICLE 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 Download citation * Received: 16 June 1995 * Accepted: 06 September 1995 * Issue Date: 01 December 1995 * DOI: https://doi.org/10.1038/ng1295-447 SHARE

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