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

• Published in: Prostate cancer and prostatic diseases Vol. 9; no. 1; pp. 62 - 67
• Main Authors: Hu, C K, McCall, S, Madden, J, Huang, H, Clough, R, Jirtle, R L, Anscher, M S
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.03.2006
• Subjects: Aged; Deactivation; Deoxyribonucleic acid; Disease Progression; DNA; DNA - genetics; DNA - metabolism; Gene polymorphism; Genetic Predisposition to Disease; Growth factors; Heterozygosity; Humans; Insulin; Insulin-like growth factor II receptors; Insulin-like growth factors; Internet; Lasers; Loss of Heterozygosity; M6P/IGF2R gene; Male; Mannose; Microdissection; Middle Aged; Mutation; Neoplasia; Nucleotides; Polymerase chain reaction; Prostate - metabolism; Prostate cancer; Prostatectomy; Prostatic Intraepithelial Neoplasia - genetics; Prostatic Intraepithelial Neoplasia - surgery; Prostatic Neoplasms - genetics; Prostatic Neoplasms - surgery; Receptor, IGF Type 2 - genetics; Tissues; Tumor suppressor genes; Tumors
• ISSN: 1365-7852; 1476-5608
• DOI: 10.1038/sj.pcan.4500842

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. 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). 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. 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.