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Loss of heterozygosity of M6P/IGF2R gene is an early event in the development of prostate cancer

Prostate Cancer and Prostatic Diseases volume 9, pages 62–67 (2006)Cite this article

Abstract

Background: The genetic events leading to initiation and/or progression of prostate cancer are not well characterized. The gene coding for the mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) has recently been identified as a tumor suppressor in several types of cancer. The purpose of the present study is to determine whether the M6P/IGF2R gene is inactivated in human prostate cancer, and if so, whether this is an early or late transformational event.

Methods: In total, 43 patients with prostate cancer treated by radical prostatectomy, with archival material available for analysis, were assessed for loss of heterozygosity (LOH) in the M6P/IGF2R gene using six different gene-specific nucleotide polymorphisms. Regions of tumor, normal prostate and premalignant high-grade prostate intraepithelial neoplasia (PIN) were identified and cells were excised by laser capture microdissection (LCM). DNA segments were amplified using polymerase chain reaction (PCR).

Results: The M6P/IGF2R gene was polymorphic in 83.7% (36/43) of patients, and 41.7% (15/36) of these informative patients had LOH in the tumor tissue. In 11/15 patients with LOH in malignant tissue, high-grade PIN could be identified, and 63.6% (7/11) also had LOH in this premalignant tissue.

Conclusions: This study is the first to find that the M6P/IGF2R gene is inactivated in prostate cancer. LOH in premalignant tissue as well suggests that mutation in the M6P/IGF2R gene is an early event in the development of prostate cancer, supporting the conclusion that it functions as a tumor suppressor gene in this disease.

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Authors and Affiliations

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

    C K Hu, H Huang, R Clough, R L Jirtle & M S Anscher

  2. Department of Pathology, Duke University Medical Center, Durham, NC, USA

    S McCall & J Madden

Authors
  1. C K Hu
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  2. S McCall
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  3. J Madden
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  4. H Huang
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  5. R Clough
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  6. R L Jirtle
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  7. M S Anscher
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Correspondence to M S Anscher.

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Hu, C., McCall, S., Madden, J. et al. Loss of heterozygosity of M6P/IGF2R gene is an early event in the development of prostate cancer. Prostate Cancer Prostatic Dis 9, 62–67 (2006). https://doi.org/10.1038/sj.pcan.4500842

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