肿瘤研究何去何从.pptVIP

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2018-10-27 发布于广东
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肿瘤研究何去何从.ppt

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Cancer Research: Where We Are? Where to Go? DEPARTMENT OF MEDICINE Science and Technology in Cancer Research Singular Discoveries: 1910 RSV, Rous (Nobel Prize 1966) 1953 DNA structure, Watson Crick (1962) 1970 Restriction enzymes, Arber, Smith Nathans (1978) 1970 Reverse transcriptase, Temin Baltimore (1975) 1970’s Cell cycle, Hartwell, Hunt Nurse (2001) 1976 v-src (first oncogene), Varmus and Bishop (1989) 1979 p53, Levine and Lane Technology Innovations: 1970 DNA sequencing, Ray Wu, expanded by Sanger Gilbert (1980) 1987 Gene knockout, Smithies, Capecchi Evans (2007) 1995 DNA microarray, Schena, Shalon Brown 1998 RNA interference, Fire Mello (2006) 2005 Next-generation sequencing 2010-13 TALEN, CRSPR-Cas9 systems Cancer Research in the Post-genomic Era DNA microarray and deep sequencing: cancer genome can be systematically explored. Enriched Information on somatic mutations. Challenges researchers face today: translating cancer genome abnormality to biological significance (heterogeneity); determining cancer “driver” genes/mutations in a certain type of lymphoma; finding out whether they are druggable. Example 1: Identification of Molecular Targets in Primary Mediastinal B-Cell (PMBL) and Hodgkin Lymphoma PMBL Molecular Similarities between Primary Mediastinal B-Cell (PMBL) and Hodgkin Lymphoma HL – Over one third of PMBL signature genes also expressed in HL – Genomic locus on chromosome band 9p24 amplified in 30-50% of PMBL and HL cases Rosenwald et al, J Exp Med 2003; Savage et al, Blood 2003 Chromosome 9p24 Amplicon in PMBL and HL Amplicon Genes and Their Expression Chr. 9p24 Amplicon Genes and Their Expression 3 Mb JAK2 INSL6 INSL4 RLN2 RLN1 C9orf46 PDL1 PDL2 KIAA1432 ERMP1 MLANA KIAA2026 RANBP6 IL33 TPD52L3 UHRF2 GLDC JMJD2C Rui et al. Cancer Cell 2010 JAK2 RANBP6 JMJD2C 9p24 shRNA library screen showed three essential genes JAK2 and JMJD2C Expression in PMBL vs DLBCL Steidl, Gascoyne shJAK2 and shJMJD2C Synergize in Killing