Porter CM, Haffner MC, Kulac I, et al. - Using a combination of methylated-DNA precipitation and methylation-sensitive restriction enzymes, and laser-capture microdissection targeted methylation analysis was done, followed by bisulfite sequencing on DNA isolated from prostate tissue samples, including both primary and metastatic disease and it was hypothesized that lactoferrin (LTF, an iron-binding protein canonically known for its innate and adaptive immune functions) expression was silenced through CpG island hypermethylation in the initial stages of prostate tumorigenesis carcinogenesis. It was reported that in high-grade prostatic intraepithelial neoplasia, primary prostate carcinoma, and metastases, the LTF CpG island is often and densely methylated. Moreover, a decoupling of lactoferrin mRNA and protein expression, comprising in lesions where LTF mRNA has presumably been silenced by CpG island methylation were reported. In conclusion, in prostate tumorigenesis, LTF mRNA expression is silenced through hypermethylation, establishing the purpose of LTF as a prostate cancer tumor suppressor gene. Similarly, across samples, the frequency at which the LTF CpG island is methylated implies that in prostate cancer initiation, it is a significant and conserved step.