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Stanley Park, Benjamin Romney, Khara Walker, Robert Pilarski, Lynn Schoenfield, Frederick Davidorf, Colleen M Cebulla, Mohamed H. Abdel-Rahman; Evaluation of Germline Variants in the Promotor Region of Macrophage Migration Inhibitory Factor (MIF) in Uveal Melanoma Patients. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3961.
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© ARVO (1962-2015); The Authors (2016-present)
Two polymorphisms, rs755622 (previously reported as -173G>C) and rs5844572 (previously reported as -794 (CATT)5-8), in the promoter region of Macrophage Migration Inhibitory Factor (MIF) gene influence the basal and/or induced transcriptional activity of MIF and have been linked to several inflammatory diseases and outcome of several cancers. We investigated the potential role of these polymorphisms in the UM.
Germline DNA was extracted from mononuclear cells at the OSU Human Cancer Genetic sample bank according to published protocol using a simple salting out procedure. A total of 163 patients were included in the study. The average age of the patients was 58 years old (range 18-86), 87 (53.4%) were males and 76 (46.6%) were females. The rs755622 variant was studied using Taqman real-time PCR and the rs5844572 using fluorescence-based genotyping. Allele frequencies were determined for both polymorphisms in the patient cohort. The allele frequency in the general population was assessed in 102 healthy adults from the same geographical location. The levels of MIF expression in the UM tumors was studied in a subset of primary tumors, as well as, tumor cell lines and normal cadaver choroid using Western blot.
The rs755622 variant was successfully assessed in 151 patients while the rs5844572 variant was assessed in all patients. The allele frequencies of the rs755622 variant were C/C (4.6%), G/C (26.5%) and G/G (68.9%). The allele frequencies of the rs5844572 variant were as follows- 5/5 (9.8%), 5/6 (35%), 5/7 (5.5%), 5/8 (0%), 6/6 (33.1%), 6/7 (14.7%), 6/8 (0%), 7/7 (1.8%), 7/8 (0%). The allele frequency for the general population showed no statistical difference from the UM cohort (data not shown). Finally, the MIF protein expression was higher in the tumors compared to the controls.
The UM sample population appears to follow a similar allelic distribution as the control population for these polymorphisms and thus does not appear to be associated with risk of UM. However, we identified higher MIF expression in the tumors than the controls with a limited tissue cohort. We are expanding the study to include additional tumors samples. The correlation between the polymorphisms and patient survival as well as tumor MIF expression, tumor somatic genetic alterations, tumor inflammatory cellular infiltrate and histology will be presented.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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