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.
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 humanprostate 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.
Authors: Lang Wu; Xiang Shu; Jiandong Bao; Xingyi Guo; Zsofia Kote-Jarai; Christopher A Haiman; Rosalind A Eeles; Wei Zheng Journal: Cancer Res Date: 2019-07-23 Impact factor: 12.701
Authors: Iona Cheng; Daniel O Stram; Noël P Burtt; Lauren Gianniny; Rachel R Garcia; Loreall Pooler; Brian E Henderson; Loïc Le Marchand; Christopher A Haiman Journal: Cancer Epidemiol Biomarkers Prev Date: 2009-05-12 Impact factor: 4.254
Authors: Helen J Huang; Laura S Angelo; Jordi Rodon; Michael Sun; Klaus-Peter Kuenkele; Henrique A Parsons; Jonathan C Trent; Razelle Kurzrock Journal: PLoS One Date: 2011-10-11 Impact factor: 3.240
Authors: Sean Harrison; Rosie Lennon; Jeff Holly; Julian P T Higgins; Mike Gardner; Claire Perks; Tom Gaunt; Vanessa Tan; Cath Borwick; Pauline Emmet; Mona Jeffreys; Kate Northstone; Sabina Rinaldi; Stephen Thomas; Suzanne D Turner; Anna Pease; Vicky Vilenchick; Richard M Martin; Sarah J Lewis Journal: Cancer Causes Control Date: 2017-03-30 Impact factor: 2.506