POSITIONAL CLONING OF ZNF217 AND NABC1 - GENES AMPLIFIED AT 20Q13.2 AND OVEREXPRESSED IN BREAST-CARCINOMA

We report here the molecular cloning of an approximate to 1-Mb region of recurrent amplification at 20q13.2 in breast cancer and other tumor s and the delineation of a 260-kb common region of amplification. Anal ysis of the I-Mb region produced evidence for five genes, ZNF217, ZNF2 18, and NABC1, PIC1L (PIC1-like), CYP24, and a pseudogene CRP (Cycloph illin Related Pseudogene). ZNF217 and NABC1 emerged as strong candidat e oncogenes and were characterized in detail. NABC1 is predicted to en code a 585-aa protein of unknown function and is overexpressed in most but not all breast cancer cell lints in which it was amplified. ZNF21 7 is centrally located in the 260-kb common region of amplification, t ranscribed in multiple normal tissues, and overexpressed in all cell l ines and tumors in which it is amplified and in two in which it is not . ZNF217 is predicted to encode alternately spliced, Kruppel-like tran scription factors of 1,062 and 1,108 aa, each having a DNA-binding dom ain (eight C2H2 zinc fingers) and a proline-rich transcription activat ion domain.