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  • Original Paper
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M6P/IGF2R is mutated in squamous cell carcinoma of the lung

Oncogene volume 19, pages 1572–1578 (2000)Cite this article

Abstract

In addition to the intracellular sorting of lysosomal enzymes, the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) plays a critical role in regulating the bioavailability of extracellular proteolytic enzymes and growth factors. It has also been shown to be mutated in a number of human cancers, and to suppress cancer cell growth. The purpose of this study was to determine if the M6P/IGF2R is mutated in lung cancer, a leading cause of cancer death worldwide. Archival pathology specimens were obtained on 22 patients with newly diagnosed, untreated squamous cell carcinoma of the lung. Two polymorphisms in the 3′-untranslated region of the M6P/IGF2R were used to screen lung tumors for loss of heterozygosity (LOH) by PCR amplification of DNA. Nineteen of 22 (86%) patients were informative (heterozygous), and 11/19 (58%) squamous cell carcinomas of the lung had LOH at the M6P/IGF2R locus. The remaining allele in 6/11 (55%) LOH patients contained mutations in either the mannose 6-phosphate or the IGF2 binding domain of the M6P/IGF2R. Thus, the M6P/IGF2R is mutated frequently in squamous cell carcinoma of the lung, providing further support for its function as a tumor suppressor.

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Acknowledgements

The authors would like to thank Hongtao Xing and Hong Huang for their assistance with data analysis, and David Pulford and Monica Bandera for M6P/IGF2R mutation confirmation. This research is supported by NIH grants CA25951 and ES08823, DOD Grant DAMD17-98-1-8305. Rohm & Haas Chemical Company, Inc., Sumitomo Chemical Company, Ltd. and Zeneca Pharmaceuticals, Ltd. For additional information on the M6P/IGF2R, visit the website: (http://www.geneimprint.com).

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Authors and Affiliations

  1. Department of Radiation Oncology, Duke University Medical Center, North Carolina, Durham, 27710, NC, USA

    Feng-Ming Kong, Mitchell S Anscher, J Keith Killian & Randy L Jirtle

  2. Department of Pathology, Vanderbilt University Medical Center, Nashville, 37232, Tennessee, TN, USA

    Mary K Washington

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  1. Feng-Ming Kong
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Kong, FM., Anscher, M., Washington, M. et al. M6P/IGF2R is mutated in squamous cell carcinoma of the lung. Oncogene 19, 1572–1578 (2000). https://doi.org/10.1038/sj.onc.1203437

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