Positional cloning of ZNF 217 and NABC 1 : Genes amplified at 20q13.2 and overexpressed in breast carcinoma

Positional cloning of ZNF217 and NABC1: Genes amplified at 20q13.2 and overexpressed in breast carcinoma

^*Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720; ^†Department of Genetics, University of Toronto, ON Canada M5G 1X8; ^§Laboratory for Cancer Genetics, Tampere University Hospital and Institute of Medical Technology, P.O. Box 2000, Fin-33521 Tampere, Finland; ^‡University of California San Francisco Cancer Center, San Francisco, CA 94143; ^‖Department of Medical Genetics, University of British Columbia, Vancouver, BC Canada V6T 2B5; ^**Laboratory of Cancer Genetics, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4470; ^‡‡Life Technologies, Inc., Rockville, MD 20850; and ^¶Brush Cancer Research Institute, California Pacific Medical Center, San Francisco, CA 94619

Edited by Janet D. Rowley, University of Chicago Medical Center, Chicago, IL, and approved April 14, 1998 (received for review January 13, 1998)

Abstract

We report here the molecular cloning of an ≈1-Mb region of recurrent amplification at 20q13.2 in breast cancer and other tumors and the delineation of a 260-kb common region of amplification. Analysis of the 1-Mb region produced evidence for five genes, ZNF217, ZNF218, and NABC1, PIC1L (PIC1-like), CYP24, and a pseudogene CRP (Cyclophillin Related Pseudogene). ZNF217 and NABC1 emerged as strong candidate oncogenes and were characterized in detail. NABC1 is predicted to encode a 585-aa protein of unknown function and is overexpressed in most but not all breast cancer cell lines in which it was amplified. ZNF217 is centrally located in the 260-kb common region of amplification, transcribed in multiple normal tissues, and overexpressed in all cell lines and tumors in which it is amplified and in two in which it is not. ZNF217 is predicted to encode alternately spliced, Kruppel-like transcription factors of 1,062 and 1,108 aa, each having a DNA-binding domain (eight C2H2 zinc fingers) and a proline-rich transcription activation domain.

Footnotes

↵ †† To whom reprint requests should be addressed at University of California San Francisco Cancer Center 2340 Sutter Street, Room N415, University of California, San Francisco, CA 94143-0808. e-mail: gray{at}cc.ucsf.edu; collins{at}cc.ucsf.edu.
This paper was submitted directly (Track II) to the Proceedings Office.
Abbreviations: FISH, fluorescence in situ hybridization; STS, sequence-tagged site; QPCR, quantitative PCR; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; EST, expressed sequence tag; BCM, Baylor College of Medicine.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF041259 and AF041260).