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

Publication ,  Journal Article
Hu, CK; McCall, S; Madden, J; Huang, H; Clough, R; Jirtle, RL; Anscher, MS
Published in: Prostate Cancer Prostatic Dis
2006

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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Published In

Prostate Cancer Prostatic Dis

DOI

ISSN

1365-7852

Publication Date

2006

Volume

9

Issue

1

Start / End Page

62 / 67

Location

England

Related Subject Headings

  • Urology & Nephrology
  • Receptor, IGF Type 2
  • Prostatic Neoplasms
  • Prostatic Intraepithelial Neoplasia
  • Prostatectomy
  • Prostate
  • Middle Aged
  • Microdissection
  • Male
  • Loss of Heterozygosity
 

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Hu, C. K., McCall, S., Madden, J., Huang, H., Clough, R., Jirtle, R. L., & Anscher, M. S. (2006). Loss of heterozygosity of M6P/IGF2R gene is an early event in the development of prostate cancer. Prostate Cancer Prostatic Dis, 9(1), 62–67. https://doi.org/10.1038/sj.pcan.4500842
Hu, C. K., S. McCall, J. Madden, H. Huang, R. Clough, R. L. Jirtle, and M. S. Anscher. “Loss of heterozygosity of M6P/IGF2R gene is an early event in the development of prostate cancer.Prostate Cancer Prostatic Dis 9, no. 1 (2006): 62–67. https://doi.org/10.1038/sj.pcan.4500842.
Hu CK, McCall S, Madden J, Huang H, Clough R, Jirtle RL, et al. Loss of heterozygosity of M6P/IGF2R gene is an early event in the development of prostate cancer. Prostate Cancer Prostatic Dis. 2006;9(1):62–7.
Hu, C. K., et al. “Loss of heterozygosity of M6P/IGF2R gene is an early event in the development of prostate cancer.Prostate Cancer Prostatic Dis, vol. 9, no. 1, 2006, pp. 62–67. Pubmed, doi:10.1038/sj.pcan.4500842.
Hu CK, McCall S, Madden J, Huang H, Clough R, Jirtle RL, Anscher MS. Loss of heterozygosity of M6P/IGF2R gene is an early event in the development of prostate cancer. Prostate Cancer Prostatic Dis. 2006;9(1):62–67.

Published In

Prostate Cancer Prostatic Dis

DOI

ISSN

1365-7852

Publication Date

2006

Volume

9

Issue

1

Start / End Page

62 / 67

Location

England

Related Subject Headings

  • Urology & Nephrology
  • Receptor, IGF Type 2
  • Prostatic Neoplasms
  • Prostatic Intraepithelial Neoplasia
  • Prostatectomy
  • Prostate
  • Middle Aged
  • Microdissection
  • Male
  • Loss of Heterozygosity