HGNC Approved Gene Symbol: ZNF217
Cytogenetic location: 20q13.2 Genomic coordinates (GRCh38): 20:53,567,071-53,597,702 (from NCBI)
Collins et al. (1998) studied the region of amplification on chromosome 20q13 that had been demonstrated by comparative genomic hybridization studies to contain copy-number gains in breast cancer and in several other forms of cancer. Analysis of a 1-Mb region of recurrent amplification produced evidence for 5 genes, of which 2, ZNF217 and NABC1 (BCAS1; 602968), emerged as strong candidate oncogenes. ZNF217 was found to be 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 was amplified and in 2 in which it was not. ZNF217 was predicted to encode alternatively spliced, Kruppel-like transcription factors of 1,062 and 1,108 amino acids, each having a DNA-binding domain containing 8 C2H2-type zinc fingers and a proline-rich transcription activation domain.
Huang et al. (2005) stated that ZNF217 proteins localize predominantly to the nucleus and associate with proteins involved in transcriptional repression.
Huang et al. (2005) showed that ZNF217 can attenuate apoptotic signals resulting from telomere dysfunction as well as from doxorubicin-induced DNA damage, and that silencing ZNF217 with siRNA restored sensitivity to doxorubicin. Elevated ZNF217 led to increased phosphorylation of Akt1 (164730), whereas inhibition of the phosphatidylinositol-3 kinase pathway and Akt phosphorylation decreased ZNF217 protein levels and increased sensitivity to doxorubicin. Huang et al. (2005) suggested that ZNF217 may promote neoplastic transformation by increasing cell survival during telomeric crisis, and may promote later stages of malignancy by increasing cell survival during chemotherapy.
Studies in which comparative genomic hybridization was used revealed approximately 20 regions of recurrent increased DNA sequence copy number in breast tumors (Kallioniemi et al., 1994; Isola et al., 1995). These regions are predicted to encode dominantly acting genes that may play a role in tumor progression or response to therapy. Three of these regions had been associated with established oncogenes: ERBB2 (164870) at 17q12, MYC (190080) at 8q24, and CCND1 (168461) and EMS1 (164765) at 11q13. In breast cancer, ERBB2 and CCND1/EMS1 amplification and overexpression are associated with decreased life expectancy, whereas MYC amplification has been associated with lymph node involvement, advanced stage, and an increased rate of relapse. Amplification at 20q13 occurs in a variety of tumor types and is associated with aggressive tumor behavior. Kallioniemi et al. (1994) found increased copy number involving 20q13 in 40% of breast cancer cell lines and 18% of primary breast tumors. Other comparative genomic hybridization studies revealed copy number gains at 20q13 in greater than 25% of cancers of the ovary, colon, head and neck, brain, and pancreas.
Collins, C., Rommens, J. M., Kowbel, D., Godfrey, T., Tanner, M., Hwang, S., Polikoff, D., Nonet, G., Cochran, J., Myambo, K., Jay, K. E., Froula, J., and 16 others. Positional cloning of ZNF217 and NABC1: genes amplified at 20q13.2 and overexpressed in breast carcinoma. Proc. Nat. Acad. Sci. 95: 8703-8708, 1998. [PubMed: 9671742] [Full Text: https://doi.org/10.1073/pnas.95.15.8703]
Huang, G., Krig, S., Kowbel, D., Xu, H., Hyun, B., Volik, S., Feuerstein, B., Mills, G. B., Stokoe, D., Yaswen, P., Collins, C. ZNF217 suppresses cell death associated with chemotherapy and telomere dysfunction. Hum. Molec. Genet. 14: 3219-3225, 2005. [PubMed: 16203743] [Full Text: https://doi.org/10.1093/hmg/ddi352]
Isola, J. J., Kallioniemi, O. P., Chu, L. W., Fuqua, S. A., Hilsenbeck, S. G., Osborne, C. K., Waldman, F. M. Genetic aberrations detected by comparative genomic hybridization predict outcome in node-negative breast cancer. Am. J. Path. 147: 905-911, 1995. [PubMed: 7573366]
Kallioniemi, A., Kallioniemi, O. P., Piper, J., Tanner, M., Stokke, T., Chen, L., Smith, H. S., Pinkel, D., Gray, J. W., Waldman, F. M. Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization. Proc. Nat. Acad. Sci. 91: 2156-2160, 1994. [PubMed: 8134364] [Full Text: https://doi.org/10.1073/pnas.91.6.2156]