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Background: 1q21.3 amplification is frequently observed in metastatic melanoma. Interleukin enhancer-binding factor 2 (ILF2) is in the 1q21.3 amplified region. The functional role of ILF2 as well as its contribution in promoting an aggressive phenotype in cutaneous metastatic melanoma is unknown. Methods: In silico analyses were performed using the TCGA SKCM dataset with clinical annotations. The results were validated in three melanoma cohort microarray datasets from the GEO database. Melanoma tissues mRNA levels were assessed by RNA in situ hybridization and protein levels were analyzed by immunohistochemistry. Four stable metastatic melanoma cell lines were established for in vitro ILF2 functional characterization. Results: Our results showed that the ILF2 copy number variation (CNV) is positively correlated with ILF2 mRNA expression (r=0.68, p Conclusion: Our study uncovered that the ILF2 and U2AF2 complex may have biological implications in controlling the mRNA stability of RAD50 and ATM in metastatic melanoma. Clinically, ILF2 amplification is associated with melanoma progression, triggers a functional downstream pathway in metastatic melanoma that promotes DNA damage repair, and increases the sensitivity to ATM inhibitors. Citation Format: Xiaoqing Zhang, Matias A. Bustos, Rebecca Gross, Romela Irene Ramos, Teh-Ling Takeshima, Gordon B. Mills, Qiang Yu, Dave S. Hoon. Interleukin enhancer-binding factor 2 amplification controls mRNA stability and enhances DNA damage response in metastatic melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3233. |
