Basic Research - Cancer(구연) Oral Session 15 / Basic Research - Cancer (Ⅱ) (O-143) Crystal A (3F) 11월29일(목) 08:00-09:00 전장유전체시퀀싱을 이용한 비염색 신세포암의 미토콘드리아 유전체 돌연변이 특성에 대한 분석 ¹KAIST 의과학대학원, ²성균관대학교 의과대학 비뇨의학교실 유지웅², 이기종¹, 강민용², 성현환², 전황균², 정병창², 전성수², 이현무², 주영석¹, 서성일² Purpose: Mutations of mitochondrial DNA rarely occur during tumorigenesis. Chromophobe renal cell carcinoma (chRCCC) is a type of kidney tumor characterized by a morphologic abnormality of mitochondria. However, there is still little research on the existence of mitochondrial mutation in chRCC and how it plays a role in tumorigenesis. Here, we investigated the mutation patterns of mitochondria genome in chRCC using low-depth sequencing technique. Materials and Methods: We evaluated 17 patients with chRCC who underwent radical nephrectomy from 2010 to 2017. Mitochondrial genomic analysis was performed by low-depth whole genome sequencing. Varscan and MToolBox analysis programs were used to search for mutations. Germline mutation information reported in MtDB, Phylotree, and Mitomap databases was used to allocate patient haplogroups and exclude germline mutations. Results: Whole genome sequencing of 17 chRCC tissues at an average depth of 1x based on whole genome revealed that the mitochondrial genome was sequenced to an average of 630x. A total of 1,206 Haplotype frequency> 0.25 mutations were found, of which 30 were mutations not reported in the database. Seven of them were identified as synonymous mutations (average of 0.41 per tumor;41%), and three were truncating mutations (average of 0.18 per tumor; 18%). Truncating mutations were specifically identified as two frameshift indel and one stop gain mutation. Conclusions: In summary, chRCC had a higher frequency of truncating mutation of mitochondrial DNA compared to other solid tumors (1-2%). This finding suggests that dysfunctional mitochondria may play an oncogenic role in tumorigenesis of chRCC, while other tumors are predicted to undergo negative selection of mitochondrial truncating mutations during tumorigenesis. Based on these results, we are performing the prospective study for evaluating mutational characteristics and associated morphological changes of mitochondria under electron microscopy. keywords : chromophobe RCC, mitochondrial mutation, whole genome sequencing