Amplification of zinc finger protein 217 gene in multiple myeloma patients as a prognostic marker

Background

Multiple myeloma (MM) is an incurable hemopoietic malignancy caused by abnormal proliferation of clonal plasma cells. In MM, a complex array of genetic and epigenetic changes leads to neoplastic transformation of plasma cells, resulting in their uncontrolled growth and secretion of large amounts of nonfunctional monoclonal antibody (known as paraprotein or M protein) into the circulation. The zinc finger protein 217 (ZNF217) is a member of the Kruppel-like family of transcription factors and contains eight predicted C
2
H
2
zinc finger motifs, as well as a region rich in proline. The ZNF217 plays a key role in eukaryotic gene regulation, and which dysregulation, is often observed in cancer. The aim of this study to detect ZNF217 by fluorescent in situ hybridization in newly diagnosed MM patients and evaluation of ZNF217 in MM patients as a prognostic marker.



Patients and methods
Case-control study included 50 newly diagnosed MM patients and 20 age- and sex- matched controls (patients with nonmalignant diseases, e.g., thrombocytopenia and hypoplasia) who were tested for ZNF217 amplification by fluorescent in situ hybridization technique. At least 200 metaphases were analyzed for each patient.


Results

ZNF217 gene copy number increase was detected in 17 (34%) MM patients [13 (26%) had gene amplification and four (8%) had gene gain of the ZNF217 gene], while 100% of the control group showed negative results with a significant difference between the two groups (
P
=0.002). According to the International Staging System stages, number of MM patients with ZNF217 gene copy number increase was more than patients with negative results at stage III (
P
=0.014). Patients with ZNF217 gene copy number had shorter survival than patients with negative results (
P
=0.058).



Conclusion
In conclusion, our results showed a significant ZNF217 gene copy number increase in MM patients. It was associated with advanced disease progression and worse overall survival.