Basic Research - Cancer(구연) Oral Session 3 / Basic Research - Cancer (Ⅱ) (O-031) Rm.201 10월 30일(수) 14:00-15:00 임상적 T1 병기의 투명신세포암 환자 중 공격적 성향을 보이는 환자군에서의 유전자적 특징 분석 ¹연세대학교 의과대학 비뇨의학교실 ²연세대학교 의과대학 병리학교실 ³경희대학교 의과대학 임상약리학교실 박지수¹, 이효정¹, 임영선¹, 김종찬¹, 장원식¹, 이승환¹, 나군호¹, 최영득¹, 조남훈², 이지현³, Ahmad Almujalhem¹, Hatem Hamed Althubiany⁴, Aalqahtani Ali A¹, 함원식¹ Introduction: Molecular characteristics of early-stage clear cell renal cell carcinomas (ccRCCs) of ≤7 cm that are associated with a poor clinical outcome are poorly understood. In this study, we used RNA sequencing (RNA-Seq) to compare aggressive early-stage ccRCCs and non-aggressive early-stage ccRCCs. Methods: Among nephrectomies performed for ccRCC of ≤7 cm conducted between January 2008 and December 2014, 24 cases composed of 12 ccRCC patients with aggressive characteristics and matching pairs of 12 ccRCC patients without aggressive characteristics were obtained. An aggressive tumor was defined as a tumor exhibiting synchronous metastasis, recurrence, or cancer-specific death. RNA-Seq was performed on 24 patients, and the frequency of mutations for six genes (PBRM1, BAP1, SETD2, KDM5C, FOXC2, and CLIP4) were analyzed. Results: RNA-Seq produced 71.68 x 10 6 reads in ccRCC with aggressive characteristics and 66.69 x 10 6 reads in ccRCC without aggressive characteristics. In total, 251 genes were differentially expressed with fold changes and p-values <0.05, and 10 genes were identified with the greatest upregulation or downregulation in aggressive ccRCC that are significant even after the adjustment. Four upregulated genes were MOCOS, RGPD8, BAIAP2L1, and DDX11. Six downregulated genes were SLC16A9, FRAS1, NPR3, AQP1, TMEM38B, and PRUNE2. Although there were no significant differences in frequency of mutations in six genes (PBRM1, BAP1, SETD2, KDM5C, FOXC2, and CLIP4), the patients with aggressive ccRCC had higher mutation frequency (2-3 times) of BAP1 KDM5C, FOXC2 and CLIP4 than the patients with non-aggressive ccRCC. Conclusions: We identified new candidate genes reflecting aggressiveness of ccRCC and validated previously identified genes that are associated with disease progression of ccRCC. These discoveries would provide a new insight into tumor biology of ccRCC and would help stratify patients with early-stage ccRCC by molecular subtyping and treat accordingly. keywords : lear cell renal cell cancer, next-generation sequencing, biomarker