세미나/행사

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제목 2023년 11월 28일 생물정보학 세미나
작성자 관리자 작성일 2023-11-23
서울대학교 생물정보학 협동과정 주최로 세미나를 아래와 같이 열고자 하오니 많은 참여 바랍니다.


세미나는 Zoom을 통한 온라인 강의로 예정되어 있으며 강의에 참여하고자 하시는 분께서는 아래의 링크로 참여 부탁드리겠습니다.


*줌으로 참석하기 위해서는 "참석자로 회의 참가" --> 이름, 성, 이메일 주소, 이메일 주소 확인을 입력하시고 등록하시면 회의 참석이 가능합니다.


일시: 2023년 11월 28일 화요일 오전 11시


연사: 김선영 교수님 (국가생명연구자원센터)



Title: Estrogen Signaling as a Putative Target for Never-Smoker Lung Adenocarcinoma Patients without EGFR Mutation and ALK Fusion from Proteogenomic Characterization

Abstract:
Never-smoker lung adenocarcinoma (NSLA) is prevalent in Asian populations, and is even more in women. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusions are major alterations observed in NSLA. We have focused on NSLA without EGFR and ALK alteration (NENA) rather than NSLA with EGFR and ALK (EA). Firstly, we selected 141 NSLA tissues, and performed proteogenomic analyses including the whole genome sequencing (WGS), transcriptome, methylation EPIC array, total proteome and phosphoproteome. We then excluded forty EA patients and seven patients with NENA microsatellite instability. Genome analysis revealed that TP53 (25%), KRAS (22%), ROS1 fusion (14%), and SETD2 (11%) were the most frequently mutated genes in NENA patients. Proteogenomic impact analysis revealed that STK11 and ERBB2 somatic mutations had broader effects on cancer-associated genes in NENA. Through DNA copy number alteration analysis, we identified 22 prognostic proteins, influencing transcriptomic and proteomic changes. Gene set enrichment analysis revealed that the estrogen signaling emerged as the key pathway activated in NENA. A lot of proteogenomic evidence supported the increased estrogen signaling, such as copy number deletions in chromosomes 14 and 21, STK11 mutation, and DNA hypomethylation of LLGL2 and ST14. Finally, saracatinib, an Src inhibitor, was suggested as a potential drug for targeting activated estrogen signaling in NENA, and was experimentally validated in vitro using cell line model. In this study, we enhanced our understanding of the etiology of NENA NSLA through the proteogenomic landscape, based on which we proposed saracatinib as an effective drug.