8p21.2

BAPX2,NKX3,NKX3.1,NKX3A

Prostate Cancer

Prostate cancer is the most commonly diagnosed cancer in American men and the second leading cause of cancer-related deaths. Prostate cancer predominantly occurs in the peripheral zone of the human prostate, with roughly 5 to 10% of cases found in the central zone. Disease development involves the temporal and spatial loss of the basal epithelial compartment accompanied by increased proliferation and dedifferentiation of the luminal (secretory) epithelial cells. Prostate cancer is a slow developing disease that is typically found in men greater than 60 years of age and incidence increases with increasing age.

PSA test combined with digital-rectal exams are used to screen for the presence of disease. If the digital-rectal exams are positive, additional tests including needle core biopsies are taken to assess disease stage and grade. Patients with localized, prostate-restricted disease are theoretically curable with complete removal of the prostate (radical prostatectomy). Patients with extra-prostatic disease are treated with hormone (androgen ablation) therapy, radiation, and/or antiandrogens; however, no curative treatments are available for nonorgan confined, metastatic disease.

Various forms of aneuploidy.

Nkx3.1 plays an essential role in normal murine prostate development. Loss of function of Nkx3.1 leads to defects in prostatic protein secretions and in ductal morphogenesis. Loss-of-function of Nkx3.1 also contributes to prostate carcinogenesis. For example, Nkx3.1 mutant mice develop prostatic dysplasia. Nkx3.1 loss potentiates prostate carcinogenesis in a Pten^+/- background. Furthermore, by a variety of mechanisms NKX3.1 expression is reduced in noninvasive and early stage human prostate cancer, suggesting that its decreased expression is one of the earliest steps in the majority of human prostate cancers.