8HumanOncologyand Pathogenesis Program,Memorial Sloan-KetteringCancerCenter,NewYork,NY 9HowardHughesMedical Institute,Memorial Sloan-KetteringCancer Center,NewYork,NY

BACKGROUND. The role of TP63 in cancer remains controversial since both oncogenic and tumor suppressive actions have been reported. p63 protein is found in the nuclei of basal cells of the normal prostate, yet it is absent in the vast majority of prostate cancer nuclei. Since a complex array of TP63 mRNA transcripts encode polypeptides with distinct functional properties, it is important to determine which forms are expressed in normal and prostate cancer tissue. METHODS. We used real-time RT-PCR to distinguish TP63 mRNA isoforms in prostate cancer cell lines (n 7), and samples from prostate cancer patients. We sequenced all TP63 exons from 20 primary tumors, 20 metastases, 28 tumor xenografts, and 7 prostate cancer cell lines. RESULTS. TP63 mRNA isoforms were present in all tumors, albeit at levels lower than in normal prostate. The most abundant N-terminal variant wasDN; the most abundant C-terminal variant was the a form. The prostate tumor cell line CWR22Rv1 contained a single G to T substitution in exon 8 that is identical to a dominant-negative DNA binding inactivation mutation occurring in patients with a congenital TP63 deficiency syndrome. One patient tumor contained a somatic mutation in exon 11. CONCLUSIONS. The pattern of TP63 mRNA expression in normal prostate tissue is retained i