The
olfactomedin 4 (OLFM4) gene is located on chromosome 13q14.3, which frequently is deleted in human
prostate cancer. However, direct genetic evidence of OLFM4 gene alteration in human
prostate cancer has not yet been obtained. In this study, we investigated the genetics,
protein expression, and functions of the OLFM4 gene in human
prostate cancer. We found overall 25% deletions within the OLFM4 gene in cancerous epithelial cells compared with adjacent normal epithelial cells that were microdissected from 31
prostate cancer specimens using
laser-capture microdissection and genomic
DNA sequencing. We found 28% to 45% hemizygous and 15% to 57% homozygous deletions of the OLFM4 gene via fluorescence in situ hybridization analysis from 44 different
prostate cancer patient samples. Moreover, homozygous deletion of the OLFM4 gene significantly correlated with advanced
prostate cancer. By using immunohistochemical analysis of 162
prostate cancer tissue array samples representing a range of Gleason scores, we found that OLFM4
protein expression correlated inversely with advanced
prostate cancer, consistent with the genetic results. We also showed that a truncated mutant of OLFM4 that lacks the
olfactomedin domain eliminated suppression of PC-3
prostate cancer cell growth. Together, our findings indicate that OLFM4 is a novel candidate tumor-suppressor gene for chromosome 13q and may shed new light on strategies that could be used for the diagnosis, prognosis, and treatment of
prostate cancer patients.