Worldwide Research Hot News ICGC by Michael D. O Neill International Cancer Genome Consortium ICGC , ICGC ICGC ICGC 2008

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QIAGEN eyes News & Topics from QIAGEN 9March 2014 Contents Worldwide Research Hot News ICGC 2 5 6 7 Pathway Application 8 11 Seminar Report 12 13 Letter from Technical Service 14 15 QIAGEN 15 Information 16 Sample & Assay Technologies

Worldwide Research Hot News ICGC by Michael D. O Neill International Cancer Genome Consortium ICGC 2008 1 50 25,000 2008 4 ICGC 5 2 50 ICGC ICGC 2008 11 11 ICGC 8 ICGC 500 ICGC 500 1 Cancer Genome Project ICGC ICGC ICGC 69 17 25,000 69 10 ICGC ICGC www.icgc.org BioMart Data Coordination Center ICGC 3 4 cholangiocarcinoma 5 6 4 4 2 www.qiagen.co.jp Issue 9/2014

Worldwide Research Hot News ICGC Thomas J. Hudson Ontario Institute for Cancer Research ICGC 2 7 ICGC Hudson NIH The Cancer Genome Atlas TCGA 8 Wellcome Trust Sanger Institute Cancer Genome Project CGP 9 ICGC Hudson ICGC DNA 50 20 Hudson 600 DNA Hudson Journal of Internal Medicine 10 2013 2013 International Journal of Cancer 11 2012 Cell 12Hudson DNA TCGA 2006 3 2 10 ICGC 8,000 ICGC Data Coordination Center ICGC DCC Hudson ICGC ICGC Issue 9/2014 Sample & Assay Technologies 3

Worldwide Research Hot News 2013 10 17 Nature 13 TCGA 12 127 TCGA ICGC INGENUITY INGENUITY 2013 4 QIAGEN TCGA Institute of Cancer Research Alan Ashworth 14 Hudson 15 Nature ICGC 2 2 INGENUITY Systems QIAGEN INGENUITY Systems www.ingenuity.com/ INGENUITY Systems IPA omics ireport RNA-Seq PCR Variant Analysis Ingenuity Knowledge Base 2013 1 INGENUITY Systems 1 INGENUITY RNA-Seq INGENUITY Systems ICGC 4 www.qiagen.co.jp Issue 9/2014

Worldwide Research Hot News 1. Cancer Genome Consortium (ICGC) Web Site. http://icgc.org/ International 2. The International Cancer Genome Consortium, International Network of Cancer Genome Projects, Nature 464:993-966 (April 15, 2010). http://www.nature.com/nature/journal/v464/n7291/abs/nature08987.html 3. Yasushi Totoki, Kenji Tatsuno, Shogo Yamamoto, et al., High-Resolution Characterization of a Hepatocellular Carcinoma Genome, Nature Genetics 43(5):464-469 (May, 2011). http://www.nature.com/ng/journal/v43/n5/abs/ng.804.html 4. Akihiro Fujimoto, Yasushi Totoki, Tetsuo Abe, et al., Whole-Genome Sequencing of Liver Cancers Identifies Etiological Influences on Mutation Patterns and Recurrent Mutations in Chromatin Regulators, Nature Genetics 44(7):760-764 (July, 2012). http://www.nature.com/ng/journal/v44/n7/abs/ng.2291.html 5. ICGC News Release (November 3, 2013). http://icgc.org/files/icgc/icgc%20news%20release%203nov2013.pdf 6. Yuchen Jiao, Timothy M. Pawlik, Robert A. Anders, et al., Exome Sequencing Identifies Frequent Inactivating Mutations in BAP1, ARID1A and PBRM1 in Intrahepatic Cholangiocarcinomas, Nature Genetics 45:1470-1473 (December, 2013). http://www.nature.com/ng/journal/v45/n12/full/ng.2813.html 7. ICGC News Release (December 4, 2012). http://icgc.org/files/icgc/icgc%20news%20release%204dec2012.pdf 8. Cancer Genome Project (CGP) Web Site. http://www.sanger.ac.uk/research/projects/cancergenome/ 9. The Cancer Genome Atlas (TCGA) Web Site. http://cancergenome.nih.gov/ 10. T.J. Hudson, Genome Variation and Personalized Cancer Medicine, J. Internal Medicine 274:440-450 (November, 2013). http://onlinelibrary.wiley.com/doi/10.1111/joim.12097/abstract 11. Ben Tran, Andrew M.K. Brown, Philippe L. Bedard, et al., Feasibiity of Real Time Net Generation Sequencing of Cancer Genes Linked to Drug Response: Results from a Clinical Trial, International Journal of Cancer 132:1547-1555 (October 1, 2013). http://onlinelibrary.wiley.com/journal/10.1002/(issn)1097-0215/issues?year=2013 12. Janet E. Dancey, Philippe L. Bedard, Nicole Onetto, and Thomas J. Hudson, The Genetic Basis for Cancer Treatment Decisions, Cell 148:409-420 (February 3, 2012). http://www.cell.com/abstract/s0092-8674(12)00020-7 13. Cyriac Kandoth, Michael D. McLellan, Fabio Vandin, et al., Mutational Landscape and Significance Across 12 Major Cancer Types, Nature 502:333-339 (October 17, 2013). http://www.nature.com/nature/journal/v502/n7471/full/nature12634.html 14. Alan Ashworth, Comparisons Across Cancers Order from Disorder Sprung, Nature 502:306 (October 17, 2013). http://www.nature.com/nature/journal/v502/n7471/full/502306a.html 15. Thomas J. Hudson, Comparisons Across Cancers A Clinical Perspective, Nature 502:306-307 (October 17, 2013). BioQuick WORLDWIDE RESEARCH HOT NEWS 30 D. BioQuick 3 UrzymeRNA Neuroscience 2013 MicroRNA pirna Neuroscience 2013 BioQuick http://qiagen.biomarket.jp/ Issue 9/2014 Sample & Assay Technologies 5

2 MDx 10 3 CDx TR EGFR EGFR KRAS CDx CDx 100 PCR GMP Good Manufacturing Practice GMP FDA 6 www.qiagen.co.jp Issue 9/2014

TR 1 TR CDx CDx 2013 CDx 2014 2013 CDx NGS TR NGS TR 大学ベンチャー企業 シーズ ニーズ 治療薬 C 開発 研究所標準化 治療薬 B 開発 製薬企業 診断薬企業 治療薬 A 開発 プロトタイプ診断薬 A 開発 治療薬開発 診断薬 Ver.1.0 治療薬開発 診断薬 Ver.2.0 薬事同時申請 承認 包括開発契約の締結 Phase I Phase II Phase III 1. Issue 9/2014 Sample & Assay Technologies 7

Pathway Application 4 1970 Unstructured uncertainty Structured uncertainty 1 1. H Bode-Shannon Bode Shannon 8 www.qiagen.co.jp Issue 9/2014

Pathway Application Elia, N., When bode meets Shannon: control-oriented feedback communication schemes, IEEE Transactions of Automatic Control, 49(9), 1477-1488, 2004; Tatikonda, S., Control under Communication Constraints, Ph.D. Thesis, MIT, 2000 2 Bode-Shannon 2. Bode-Shannon theorem Bode-Shannon NFB 50 Glucose Floor Glucose Ceiling 3 Kitano, et al., Metabolic Syndrome 3. Issue 9/2014 Sample & Assay Technologies 9

Pathway Application and Robustness Tradeoffs, Diabetes, 53, S6-S15, 2004 4 4. Controllability 2 Barabasi Liu, Y-Y., Slotine, J-J., Barabasi, A-L., Controllability of Complex Networks, Nature, 473, 167-173, 2011 Barabsi Crespo, et al., Gene regulatory network analysis supports inflammation as a key neurodegeneration process in prion disease, BMC Systems Biology, 6:132 2012 Controllability analysis APP Amyloid Beta Mizuno, et al., AlzPathway: a comprehensive map of signaling pathways of Alzheimer s disease, BMC Systems Biology, 6:52 2012 5 10 www.qiagen.co.jp Issue 9/2014

Pathway Application 5. AlzPathway Controllability Analysis Complex Systems Ilya Prigogine G. I. 1980 BZ Belousov-Zhabotinsky Reaction BZ Issue 9/2014 Sample & Assay Technologies 11

Seminar Report 2003 10 99 99.99 10 SNPs GWAS DNA 1980 1,000 2 1.4 10 10 1 10 GWAS 1,000 SNPs SNPs 5 6,700 1 1.5 2007 100 RNA DNA 1 SNPs 12 www.qiagen.co.jp Issue 9/2014

Seminar Report NIH 1,000 1,000 NIH NCBI GenBank EMBL DNA EU SPIDIA NCBI EMBL DNA DDBJ BBJ DNA 30 NCBN 2013 12 JPDSC 1 9 2 JPDSC 1. DNA 2. 3. DNA 4. 5. 6 2009 JPDSC DNA Issue 9/2014 Sample & Assay Technologies 13

Letter from Technical Service Spotlight on Expertise FFPE Q FFPE DNA RNA A DNA RNA AllPrep FFPE AllPrep DNA/RNA FFPE Kit FFPE AllPrep DNA/RNA FFPE Kit microrna 18 nt RNA FFPE FAQ Tips! FAQ QIAGEN www.qiagen.co.jp AllPrep DNA/ RNA FFPE KitCat. no. FAQ 14 www.qiagen.co.jp Issue 9/2014

Letter from Technical Service QIAGEN Did you know? Supplementary Protocol User Developed Protocol Q FFPE DNA A QIAamp DNA FFPE Tissue Kit Cat. no. 56404 Deparaffinization Solution Cat. no. 19093 Supplementary Protocol QIAGEN QIAGEN Supplementary Protocol QSP User Developed Protocol UDPQSP UDP * QSP UDP 1. QIAGEN www.qiagen.co.jp Deparaffinization Solution Cat. no. 19093 2. Supplementary Protocol User Developed Protocol * E-mail techservice-jp@qiagen.com QIAGEN FFPE DNA mirna RNA AllPrep DNA/RNA FFPE Kit FFPE? DNA RNA FFPE RNA Human Cell Cycle RT 2 Profile PCR Array 1 MDA Multiple Displacement Amplification 2 OmniScript Reverse Transcriptase 3 QuantiTect Reverse Transcriptase 4 RT 2 FFPE PreAMP www.qiagen.co.jp AllPrep DNA/RNA FFPE Kit QIAGEN epromo-jp@qiagen.com 30 2014 5 9 QIAGEN 3 DNA Issue 9/2014 Sample & Assay Technologies 15

Information mirna FFPE QIAGEN n mirna mirna n FFPE FFPE n 1 n URL n mirna https://jp.surveymonkey.com/s/mirnacore n FFPE https://jp.surveymonkey.com/s/ffpecore QIAGEN QIAGEN www.qiagen.com/knowledge-and-support/webinars/ QIAGEN www.qiagen.co.jp Trademarks and Disclaimers QIAGEN Handbook User Manual www.qiagen.co.jp Trademarks: QIAGEN, QIAamp, AllPrep, OmniScript, QuantiTect (QIAGEN Group); INGENUITY, ireport (INGENUITY Corporation). 2302199 02/2014 2014 QIAGEN, all rights reserved www.qiagen.co.jp n 104-0054 n 3-13-1 n Forefront Tower II Tel:03-6890-7300 n Fax:03-5547-0818 n E-mail:techservice-jp@qiagen.com Sample & Assay Technologies