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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Hu, CK; McCall, S; Madden, J; Huang, H; Clough, R; Jirtle, RL; Anscher, MS

Published Date

  • 2006

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 62 - 67

PubMed ID

  • 16304558

International Standard Serial Number (ISSN)

  • 1365-7852

Digital Object Identifier (DOI)

  • 10.1038/sj.pcan.4500842


  • eng

Conference Location

  • England