| 대한안과학회 학술대회 발표 연제 초록 |
| 포도막 F-002 |
| 포도막흑색종에서 MYC pathway의 역할 |
연세대학교 의과대학 안과학교실 |
| 김용준, 이성철, 이승규 |
목적 : Uveal melanoma (UVM) is the most common intraocular tumor in adults. Despite advances in chemotherapy, the 1-year survival rate of metastatic UVM remains approximately 15%. The mechanisms involving intrinsic chemoresistance of metastatic UVM, and the relevant therapeutic targets for UVM remain elusive. 방법 : Cohorts of 80 and 67 patients diagnosed with, and treated for, primary UVM and skin cutaneous melanoma (SKCM), respectively, using The Cancer Genome Atlas dataset, were compared. The most relevant clinicopathological information and survival data were reviewed. Mutational burden, mutational signatures, and oncogenic signatures enriched in UVMs and SKCMs were analyzed using whole exome and transcriptome sequencing data. A kinome-wide siRNA library screening was conducted to identify relevant therapeutic targets. 결과 : Mutational burdens identified by whole exome sequencing were significantly lower in UVM than in SKCM patients (medians: 19.0 vs. 321.0, respectively; P < 0.001). Transcriptome analysis revealed that the MYC signature was more enriched in UVM patients, as compared to SKCM patients. Fifty-nine (73.8%) of 80 UVM patients showed gains in MYC copy number, and a high MYC copy number was associated with aggressive clinicopathological features of tumors, with poor survival. Notably, our screening identified WEE1, a synthetic lethal target for MYC amplification, as a therapeutic target for UVM. 결론 : Whole-exome and transcriptome analyses identified UVM as a MYC-driven cancer. Together with results of the kinome-wide siRNA library screening, we suggest that WEE1 may be an effective target for UVM patients harboring MYC amplifications. |