서울대학교 생물정보연구소와 생물정보학 협동과정 공동 주최로 특별 세미나를 아래와 같이 열고자 하오니, 많은 참여 바랍니다.

일시: 2016년 9월 21일 수요일 오전 11시

연사: 김태민 (가톨릭의과대학 의료정보학교실)

장소: 서울대학교 25동 411호

Title: Issues in identifying driver mutations in cancer genomes

Abstract: Various types of somatic aberrations are observed in human cancer genomes from small-scale nucleotide substitutions to chromosomal-level copy number changes and rearrangements. Although a majority of them are functionally neutral (passengers), some of those changes can play a key role in the development and progression of the diseases (drivers). One of major challenges in cancer genomics is how to distinguish 'cancer drivers' from 'passengers' with respect to the personalized (targeted) cancer diagnostics and therapeutics. Although recent advance in sequencing technologies - massively paralleled sequencing or next-generation sequencing (NGS) has facilitated the genome- or exome-wide screening of genomic alterations, it is still largely elusive how to identify the recurrent and potentially driving mutations or to identify actionable changes for personalized cancer therapeutics. In this talk, it will be reviewed as to how the efforts of driver identification have evolved with potential problems of current data-driven manners. Then, the recently recognized long-tail distribution of clonal frequency (in individual genomes) or population frequency of mutations (across individual genomes) will be discussed with their potential impacts on personalized cancer medicine. The findings from the evolutionary perspectives on cancer genomes will be also discussed to demonstrate how the intra- and inter-tumor heterogeneity will affect the accurate identification of Achilles heel, or early addicted oncogenic drivers in the cancer genomes.

Professional Career

Selected Publications

1. Lim CH, Cho YK, Kim SW, Choi MG, Rhee JK, Chung YJ, Lee SH, KimTM.The chronological sequence of somatic mutations in early gastric carcinogenesis inferred from multiregion sequencing of gastric adenomas. Oncotarget, In press.

2. Young-Ho Kim, Eun-Kyung Hong, Sun-Young Kong, Sung-Sik Han, Seoung-Hoon Kim, Je-Keun Rhee, Soo-Kyung Hwang, Sang-Jae Park, Tae-MinKim.Two classes of intrahepatic cholangiocarcinoma defined by relative abundance of mutations and copy number alterations. Oncotarget, In press.

3. Huang KK, Jang KW, Kim S, Kim HS, Kim SM, Kwon HJ, Kim HR, Yun HJ, Ahn MJ, Park KU, Ramnarayanan K, McPherson JR, Zhang S, Rhee JK, Vettore AL, Das K, Ishimoto T, Kim JH, Koh YW, Kim SH, Choi EC, Teh BT, Rozen SG, KimTM*,TanP*,ChoBC*.Exome sequencing reveals recurrent REV3L mutations in cisplatin-resistant squamous cell carcinoma of head and neck. Sci Rep. 2016 Jan 21;6:19552. doi: 10.1038/srep19552. PubMed PMID: 26790612; PubMed Central PMCID: PMC4726344. (*co-correspondence)

4. KimTM,AnCH,RheeJK,JungSH,LeeSH,BaekIP,KimMS,LeeSH,ChungYJ.Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma. Oncotarget. 2015 Sep 29;6(29):27725-35. doi: 10.18632/oncotarget.4834. PubMed PMID: 26336987; PubMed Central PMCID: PMC4695021.

5. Kim TM, Jung SH, An CH, Lee SH, Baek IP, Kim M, Park SW, Rhee JK, Lee SH, Chung YJ. Subclonal genomic architectures of primary and metastatic colorectal cancer based on intratumoral genetic heterogeneity. Clin Cancer Res. 2015 Oct 1;21(19):4461-72. Pubmed

6. Park RW*, KimTM*,KasifS,ParkPJ. Identification of rare germline copy number variations over-represented in five human cancer types. Mol Cancer. 2015 Feb 3;14(1):25. (*equal contribution) Pubmed

7. KimTM,ParkPJ.A genome-wide view of microsatellite instability: old stories of cancer mutations revisited with new sequencing technologies. Cancer Res. 2014 Nov 15;74(22):6377-6382. Pubmed

8. KimTM,JungSH,KimMS,BaekIP,ParkSW,LeeSH,LeeHH,KimSS,ChungYJ,LeeSH.The mutational burdens and evolutionary ages of early gastric cancers are comparable to those of advanced gastric cancers. J Pathol. 2014 Nov;234(3):365-74 Pubmed

9. KimTM,JungSH,BaekIP,LeeSH,ChoiYJ,LeeJY,ChungYJ,LeeSH.Regional Biases in Mutation Screening Due to Intratumoral Heterogeneity of Prostate Cancer. J Pathol. 2014 Aug;233(4):425-35 Pubmed

10. Kim TM, Laird PW, Park PJ. The Landscape of Microsatellite Instability in Colorectal and Endometrial Cancer Genomes. Cell. 2013 Nov 7;155(4):858-68 Pubmed

11. Kim TM, Lee SH, Chung YJ. Clinical applications of next-generation sequencing in colorectal cancers. World J Gastroenterol. 2013 Oct 28;19(40):6784-6793 Pubmed

12. Kim TM, Xi R, Luquette LJ, Park RW, Johnson MD, Park PJ. Functional genomic analysis of chromosomal aberrations in a compendium of 8000 cancer genomes. Genome Res. 2013 Feb; 23(2):217-27 Pubmed

13. Kim TM, Ramires V, Barrera-Chimal J, Bobadilla NA, Park PJ, Vaidya VS. Gene expression analysis reveals the cell cycle and kinetochore genes participating in renal ischemia reperfusion injury and early development in kidney. PLoS One. 2011;6(9):e25679. Epub 2011 Sep 28. Pubmed

14. Kim TM, Ha SA, Kim HK, Yoo J, Kim S, Yim SH, Jung SH, Kim DW, Chung YJ, Kim JW. Gene expression signatures associated with the in vitro resistance to two tyrosine kinase inhibitors, nilotinib and imatinib. Blood Cancer Journal (2011) 1, e32; doi:10.1038/bcj.2011.32 Pubmed

15. Kim TM, Huang W, Park R, Park PJ, Johnson MD. A developmental taxonomy of glioblastoma defined and maintained by microRNAs. Cancer Res. 2011 May 1;71(9):3387-99. Epub 2011 Mar 8. Pubmed

16. Kim TM, Park PJ Advances in analysis of transcriptional regulatory networks. Wiley Interdiscip Rev Syst Biol Med. 2011 Jan-Feb;3(1):21-35. Pubmed

17. Kim TM, Luquette LJ, Xi R, Park PJ rSW-seq: algorithm for detection of copy number alterations in deep sequencing data. BMC Bioinformatics. 2010; 11:432. Pubmed

18. Yim SH, KimTM*,HuHJ,KimJH,KimBJ,LeeJY,HanBG,ShinSH,JungSH,ChungYJ(*equallycontributed)Copy number variations in East-Asian population and their evolutionary and functional implications. Hum Mol Genet. 2010; 19(6):1001-8. Pubmed

19. Kim TM, Yim SH, Jeoung YB, Jung YC, Chung YJ PathCluster: a framework for gene set-based hierarchical clustering. Bioinformatics. 2008; 24:1957-8 PubMed

20. Kim TM, Yim SH, Jung YC, Park CK, Choi JY, Park WS, Kwon MS, Fiegler H, Carter NP, Rhyu MG, Chung YJ. Clinical implication of recurrent copy number alterations in hepatocellular carcinoma and putative oncogenes in recurrent gains on 1q Int J Cancer. 2008; 123(12):2808-15 PubMed

21. Kim TM, Yim SH, Chung YJ. Copy number variations in the human genome: potential source for the individual diversity and disease association studies (Review). Genomics and Informatics. 2008; 6(1):1-7 Journal Link

22. Kim TM, Jung YC, Rhyu MG, Jung MH, Chung YJ. GEAR: Genomic Enrichment Analysis of Regional DNA copy number changes. Bioinformatics. 2008; 24:420 PubMed

23. Kim TM, Chung YJ, Rhyu MG, Jung MH. Inferring biological functions and associated transcriptional regulators using Gene Set Expression Coherence Analysis (GSECA). BMC Bioinformatics. 2007; 8:453 PubMed

24. Kim TM, Chung YJ, Rhyu MG, Jung MH. Genome-wide germline methylation patterns inferred from local nucleotide frequency of repetitive sequences in human genome. Mamm Genome. 2007 Apr;18(4):277-85. PubMed

25. Kim TM, Jung MH. Identification of transcriptional regulators using Binding Site Enrichment Analysis (BSEA). In Silico Biol. 2006. 6:0049. PubMed

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