서울대학교 생물정보학 협동과정 주최로 세미나를 아래와 같이 열고자 하오니 많은 참여 바랍니다.

일시:　2019년 4월 9일 화요일 오전 11시

연사: 주영석 교수님　(카이스트 의과학대학원)

장소:　서울대학교　221동 113호

TITLE

Tracing Oncogene Rearrangements in the Mutational History of Lung Adenocarcinoma

ABSTRACT

Mutational processes giving rise to lung adenocarcinomas (LADCs) in non-smokers remain elusive. We analyzed 138 LADC whole-genomes, including 83 cases with minimal contribution of smoking-associated mutational signature. Genomic rearrangements were not correlated with smoking-associated mutations and frequently served as driver events of smoking signature-low LADCs. Complex genomic rearrangements, including chromothripsis and chromoplexy, generated 74% of known fusion oncogenes, including EML4−ALK, CD74−ROS1, and KIF5B−RET. These fusion oncogene-associated rearrangements were frequently copy number-balanced unlike other collateral rearrangements, representing a genomic signature of early oncogenesis. Mutation timing analysis revealed that fusions and point mutations of canonical oncogenes were often acquired in the early decades of life. During a long latency, cancer-related genes were disrupted or amplified by complex rearrangements. The genomic landscape was different between subgroups—EGFR-mutant LADCs had frequent whole-genome duplications with p53 mutations, whereas fusion oncogene-driven LADCs had frequent mutations in another tumor suppressor gene. Our study highlights LADC oncogenesis driven by endogenous mutational processes.