VICTOR E. VELCULESCU, M.D., Ph.D.
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`CURRENT POSITION
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` CURRICULUM VITAE
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`Co-Director of Cancer Biology
`Professor of Oncology and Pathology
`Affiliate Faculty, McKusick-Nathans Institute of Genetic Medicine
`Affiliate Faculty, Institute of Computational Medicine
`Affiliate Faculty, Bloomberg~Kimmel Institute for Cancer Immunotherapy
`Sidney Kimmel Comprehensive Cancer Center
`Johns Hopkins University School of Medicine
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`ADDRESS
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`Johns Hopkins Kimmel Cancer Center
`David H. Koch Cancer Research Building
`1550 Orleans Street, Rm. 544
`Baltimore, MD 21287
`Tel.
`(410) 955-7033
`FAX
`(410) 502-5742
`email
`velculescu@jhmi.edu
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`PERSONAL INFORMATION
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`Date of Birth:
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` August 16, 1970
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`EDUCATION
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`1988 – 1992
`1992 – 1999
`1992 – 1999
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`1999 – 2001
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`Bachelor of Science, B.S., Biological Sciences, Stanford University
`Doctor of Medicine, M.D., Johns Hopkins University School of Medicine
`Doctor of Philosophy, Ph.D., Human Genetics and Molecular Biology,
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`Johns Hopkins University School of Medicine
`Postdoctoral Fellowship in Oncology, Johns Hopkins University
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`School of Medicine
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`PROFESSIONAL EXPERIENCE
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`Undergraduate Research, Departments of Biochemistry and Pathology,
`1989 – 1992
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`Stanford University School of Medicine
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`Graduate Research, Johns Hopkins University School of Medicine
`1993 – 1998
`Postdoctoral Fellowship, Johns Hopkins Oncology Center
`1999 – 2001
`Assistant Professor of Oncology
`2002 – 2006
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`Johns Hopkins University School of Medicine
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`2003 – present Affiliate Faculty, McKusick-Nathans Institute of Genetic Medicine
`2004 – 2013
`Director, Cancer Genetics, Ludwig Center at Johns Hopkins
`2006 – 2011
`Associate Professor of Oncology,
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`Johns Hopkins University School of Medicine
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`VICTOR E. VELCULESCU, M.D., Ph.D.
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`2008 – present Affiliate Faculty, Biochemistry and Molecular Biology Department
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`Johns Hopkins University Bloomberg School of Public Health
`2009 – present Co-Director of Cancer Biology,
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`Johns Hopkins Kimmel Cancer Center
`2011 – present Professor of Oncology, Johns Hopkins University School of Medicine
`2013 – 2016
`Board of Directors, American Association of Cancer Research
`2014 – present Professor of Pathology, Johns Hopkins University School of Medicine
`2015 – present Affiliate Faculty, Institute of Computational Medicine, Johns Hopkins
`University
`2015 – present Co-Leader, Stand Up to Cancer Colorectal Cancer Dream Team
`2016 – present Affiliate Faculty, Bloomberg~Kimmel Institute for Cancer Immunotherapy,
`Johns Hopkins University School of Medicine
`2016 – present Co-Leader, Lung and Head and Neck Cancer Program, Bloomberg~Kimmel
`Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine
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`AWARDS AND HONORS
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`1989
`1992
`1992
`1992
`1996
`1998
`1999
`2000
`2001
`2001
`2003
`2004
`2004
`2006
`2007
`2008
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`2009
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`2009
`2011
`2011
`2013
`2013
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`2014
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`2014
`2014
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`President's Award for Academic Excellence, Stanford University
`Firestone Medal for Excellence in Research, Stanford University
`Graduated with Honors and Distinction, Stanford University
`Medical Scientist Training Program Fellowship, Johns Hopkins University
`Dynal Literature Award, Dynal Biotech
`Michael Shanoff Research Award, Johns Hopkins University School of Medicine
`International Grand Prize Winner, Amersham & Science Young Scientist Prize
`Order of Merit - Cavalier, President of Romania
`Benjamin Baker Scholar Award, Johns Hopkins University School of Medicine
`“Ten Future American Classics”, Biography magazine
`“Brilliant Ten Young Scientists of the Year", Popular Science
`Fellow, World Technology Award for Health and Medicine
`Pew Scholar Award, The Pew Charitable Trusts
`Sir William Osler Young Investigator Award, Interurban Clinical Club
`Judson Daland Prize, American Philosophical Society
`European Association of Cancer Research and Carcinogenesis Young Investigator
`Award
`American Association of Cancer Research Award for Outstanding Achievement in
`Cancer Research
`National Brain Tumor Society Founders Award
`Paul Marks Prize for Cancer Research, Memorial Sloan-Kettering Cancer Center
`Election to Sir William Osler Interurban Clinical Club
`Election as Honorary Member of the Academy of Medical Sciences in Romania
`American Association of Cancer Research Team Science Award for Pancreatic
`Cancer Research
`American Association of Cancer Research Team Science Award for Malignant Brain
`Tumor Research
`Election to Alpha Omega Alpha Honor Medical Society
`Highly Cited Researcher by Thompson Reuters ISI
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`VICTOR E. VELCULESCU, M.D., Ph.D.
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`2014
`2014
`2015
`2016
`2017
`2017
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`2018
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`Ad Astra Prize for Excellence in Research in the Life Sciences
`Election to American Society for Clinical Investigation (ASCI)
`Co-Leader, Stand Up to Cancer Colorectal Cancer Dream Team
`Ernst and Young Entrepreneur of the Year Award for Maryland
`Election as Foreign Honorary Member of the Romanian Academy
`American Association of Cancer Research Team Science Award for Research in
`Liquid Biopsies for Cancer
`Election to American Association of Physicians (AAP)
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`RESEARCH ACTIVITIES
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`Contribution to Science
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`Dr. Velculescu is the first, corresponding, or co-corresponding author on papers cited below.
`Source of citation information: Google Scholar as of March 24, 2018
`Total citations: 81,994
`h-index: 98
`
`1. Development of new methods for genomic analyses of human cancer. Comprehensive
`genomic analyses provide the basis for our current understanding of cancer. At the time we began
`our molecular studies in the early 1990’s essentially all analyses in cancer were performed one
`gene at time. In 1995, we developed SAGE (serial analysis of gene expression), a gene expression
`technology that allowed for global and quantitative measurement of gene activity. We applied this
`approach to provide the first insights into gene expression patterns in eukaryotic cells and to
`identify dysregulated gene expression patterns in human cancer. Through these studies we coined
`the term “transcriptome" in 1997 to describe the comprehensive gene expression patterns that
`could now be analyzed in human cancer and other cells. This approach has provided the basis for
`next-generation transcript sequencing methods used for genome-wide expression analyses (e.g.
`RNAseq). In parallel, our group has developed technologies for characterizing the cancer genome.
`These have included development of Digital Karyotyping, which allowed for quantitative
`characterization of amplifications and deletions at the DNA level in an unbiased manner. In
`subsequent years, variations of these approaches have been widely used to analyze genomic
`alterations in human cancer and other human diseases.
`a. Velculescu VE, Zhang L, Vogelstein B, Kinzler KW. Serial analysis of gene expression.
`Science 1995; 270:484-487. 5354 citations.
`b. Velculescu VE, Zhang L, Zhou W, Vogelstein J, Basrai MA, Bassett D Jr, Hieter P,
`Vogelstein B, Kinzler KW. Characterization of the yeast transcriptome. Cell 1997;88:243-
`251. 1255 citations.
`c. Velculescu VE, Madden SL, Zhang L, Lash AE, Yu J, Rago C, Lal A, Wang CJ, Beaudry
`GA, Ciriello KM, Cook BP, Dufault MR, Ferguson AT, Gao Y, He TC, Hermeking H,
`Hiraldo SK, Hwang PM, Lopez MA, Luderer HF, Mathews B, Petroziello JM, Polyak K,
`Zawel L, Zhang W, Zhang X, Zhou W, Haluska FG, Jen J, Sukumar S, Landes GM,
`Riggins GJ, Vogelstein B, Kinzler KW. Analysis of human transcriptomes. Nature
`Genetics 23: 387-8, 1999. 850 citations.
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`d. Wang TL, Maierhofer C, Speicher MR, Lengauer C, Vogelstein B, Kinzler KW,
`Velculescu VE. Digital karyotyping. Proc Natl Acad Sci USA 2002;99:16156-16161.
`236 citations.
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`2. Discovery of the role of PIK3CA in human cancer. Using the genomic tools we had
`developed, our group performed the first sequence analyses of entire gene families in a human
`cancer, initially focusing on genes involved in signal transduction pathways. These included the
`entire set of tyrosine kinases, the serine/threonine kinases, the protein phosphatases, and lipid
`kinases. Through these analyses, we identified a variety of genes not previously known to be
`involved in human cancer. In particular, we identified a high frequency of sequence alterations in
`the PIK3CA gene in colorectal, breast, brain and other cancer types. These analyses and
`subsequent studies have identified PIK3CA as one of the most highly mutated genes in human
`cancer. We showed that mutations of PIK3CA are activating, promote cellular survival and
`invasion, and that cancer cells with these alterations can be inhibited with PI3K inhibitors. Due to
`its widespread involvement in human cancer, PIK3CA is one of the most frequently targeted
`proteins in current clinical trials.
`a. Bardelli A, Parsons DW, Silliman N, Ptak J, Szabo S, Saha S, Markowitz S, Willson JK,
`Parmigiani G, Kinzler KW, Vogelstein B, Velculescu VE. Mutational analysis of the
`tyrosine kinome. Science 300:949, 2003. 510 citations.
`b. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell
`SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE.
`High frequency of mutations of the PIK3CA gene in human cancers. Science
`2004;304:554. 2971 citations.
`c. Parsons DW, Wang TL, Samuels Y, Bardelli A, Cummins JM, DeLong L, Silliman N,
`Ptak J, Szabo S, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Lengauer C,
`Velculescu VE.
` Colorectal cancer: mutations in a signalling pathway. Nature
`2005;436:792. 562 citations.
`d. Samuels Y, Diaz LA Jr, Schmidt-Kittler O, Cummins JM, Delong L, Cheong I, Rago C,
`Huso DL, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE. Mutant PIK3CA
`promotes cell growth and invasion of human cancer cells. Cancer Cell 7(6):561-73, 2005.
`800 citations.
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`3. Genome-wide analyses of human cancer. Our group working with colleagues at Johns
`Hopkins and other institutions, performed the first sequence analysis of the coding genome in
`human cancers, including in breast, colorectal, brain, pancreatic, head and neck, and ovarian
`cancers. These anlayses provide insights into the complexity of alterations in human cancer and
`identified changes in genes not previously known to be involved in these diseases. These included
`the IDH1 and IDH2 genes in gliomas, chromatin modifying genes MLL2, MLL3 and ARID1 in
`medulloblastomas, ovarian cancers, and neuroblastomas, and NOTCH1 alterations in head and
`neck cancers. In addition to inhibitors targeting PIK3CA and IDH which are already in clinical
`trials, we have begun to translate these analyses to the clinic, providing insights into the actionable
`genome as well as identifying alterations that affect response and resistance to therapuetic
`intervention.
`a. Sjöblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber T, Mandelker D, Leary RJ,
`Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J,
`Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH,
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`Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE. The
`Consensus Coding Sequences of Human Breast and Colorectal Cancers. Science.
`314(5797):268-74, 2006. 3263 citations.
`b. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, … Marie SK, Shinjo SM, Yan H,
`Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B,
`Velculescu VE, Kinzler KW. An integrated genomic analysis of human glioblastoma
`multiforme. Science 2008;321:1807-12. PMCID: 2820389. 4185 citations.
`c. Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, Fakhry C, Xie
`T-X, Zhang J, Wang J, Zhang N, El-Naggar AK, Jasser SA, Weinstein JN, Treviño L,
`Drummond JA, Muzny DM, Wu Y, Wood LD, Hruban RH, Westra WH, Koch WM,
`Califano JA, Gibbs RA, Sidransky S, Vogelstein B, Velculescu VE, Papadopoulos N,
`Wheeler DA, Kinzler KW, Myers JN. Exome Sequencing of Head and Neck Squamous
`Cell Carcinoma Reveals Inactivating Mutations in NOTCH1. Science, 333:1154-1157,
`2011. PMCID: PMC3162986. 1165 citations.
`d. Anagnostou V, Smith KN, Patrick PM, Niknafs N, Bhattacharya R, White J, Zhang T,
`Adleff V, Phallen J, Wali N, Hruban C, Guthrie VB, Rodgers K, Naidoo J, Kang H,
`Sharfman W, Georgiades C, Verde F, Illei P, Li QK, Gabrielson E, Brock MV, Zahnow
`CA, Baylin SB, Scharpf R, Brahmer JR, Karchin R, Pardoll DM and Velculescu, VE.
`Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell
`lung cancer. Cancer Discovery, 7(3):264-276, 2017. PMID: 28031159.
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`4. Liquid biopsies for non-invasive detection and characterization of human cancer. In order
`to translate our genomic efforts to diagnostic applications, we have developed approaches for
`detection of mutated DNA in the circulation of cancer patients. For this purpose, we have
`invented PARE (personalized analysis of rearranged ends) for personalized development of
`genomic biomarkers for tumor detection and monitoring. Using these approaches, we performed
`the first whole-genome analyses for detection of circulating tumor DNA, providing a universal
`approach for non-invasive detection of human cancer. More recently we developed approaches
`for direct detection of early stage cancers using circulating tumor DNA. These approaches have
`wide-spread applications in human cancer including in identification of actionable alterations,
`disease monitoring, therapeutic resistance, detection of residual disease, and early detection.
`a. Leary RJ, Kinde I, Diehl F, Schmidt K, Clouser C, Duncan C, Antipova A, Lee C,
`McKernan K, de la Vega, F, Kinzler KW, Vogelstein B, Diaz LA Jr, Velculescu VE.
`Development of Personalized Tumor Biomarkers Using Massively Parallel Sequencing.
`Science TM, 2: 20ra14, 2010. PMCID: PMC2858564. 394 citations.
`b. Leary RJ, Sausen M, Kinde I, Papadopoulos N, Carpten JD, Craig D, O'Shaughnessy J,
`Kinzler KW, Parmigiani G, Vogelstein B, Diaz LA Jr, Velculescu VE. Detection of
`Chromosomal alterations in the circulation of cancer patients with whole-genome
`sequencing. Science TM. 4:162ra154, 2012 PMCID: PMC3641759. 357 citations.
`c. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H,
`Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Lee CC,
`Fecher LA, Gallia GL, Gibbs P, Le D, Giuntoli RL, Goggins M, Hogarty MD, Holdhoff
`M, Hong SM, Jiao Y, Juhl HH, Kim JJ, … Velculescu VE, Kinzler KW, Vogelstein B,
`Papadopoulos N, Diaz LA Jr. Detection of circulating tumor DNA in early- and late-stage
`human malignancies.
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`TM.
`2014
`Feb
`19;6(224):224ra24.
`doi:
`Science
`10.1126/scitranslmed.3007094. 1289 citations.
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`d. Phallen J, Sausen M, Adleff V, Leal A, Hruban C, White J, Anagnostou V, Fiksel J,
`Cristiano S, Papp E, Speir S, Reinert T, Orntoft MW, Woodward BD, Murphy D, Parpart-
`Li S, Riley D, Nesselbush M, Sengamalay N, Georgiadis A, Li QK, Madsen MR,
`Mortensen FV, Huiskens J, Punt C, van Grieken N, Fijneman R, Meijer G, Husain H,
`Scharpf RB, Diaz LA Jr, Jones S, Angiuoli S, Ørntoft T, Nielsen HJ, Andersen CL,
`Velculescu VE. Direct detection of early-stage cancers using circulating tumor DNA.
`Science TM. 2017 Aug 16;9(403). pii: eaan2415. doi: 10.1126/ scitranslmed.aan2415.
`PMID: 28814544.
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`List of Publications in NCBI MyBibliography:
`http://www.ncbi.nlm.nih.gov/sites/myncbi/victor.velculescu.1/bibliography/41165259/public/?sort
`=date&direction=descending
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`Complete List of Peer Reviewed Publications:
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`El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer
`WE, Kinzler KW, Vogelstein B. WAF1, a potential mediator of p53 tumor suppression.
`Cell 75: 817-825, 1993.
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`Dintzis SM, Velculescu VE, Pfeffer SR. Receptor extracellular domains may contain
`trafficking information - studies of the 300-kDa mannose 6-phosphate receptor. Journal
`of Biological Chemistry 269: 12159-12166, 1994.
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`El-Deiry WS, Harper JW, O'Connor PM, Velculescu VE, Canman CE, Jackman J,
`Pietenpol JA, Burrell M, Hill DE, Wang Y, Wiman KG, Mercer WE, Kastan MB, Kohn
`KW, Elledge SJ, Kinzler KW, Vogelstein B. WAF1/CIP1 is induced in p53 mediated
`G1 arrest and apoptosis. Cancer Research 54: 1169-1174, 1994.
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`El-Deiry WS, Tokino T, Waldman T, Oliner JD, Velculescu VE, Burrell M, Hill DE,
`Healy E, Rees JL, Hamilton SR, Kinzler KW, Vogelstein B. Topological control of
`p21WAF1/CIP1 expression in normal and neoplastic tissues. Cancer Research 55: 2910-19,
`1995.
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`Velculescu VE, Zhang L, Vogelstein B, Kinzler KW. Serial analysis of gene expression.
`Science 270: 484-487, 1995.
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`Velculescu VE and El-Deiry WS. Biological and clinical implications of the p53 tumor
`suppressor gene. Clinical Chemistry 42: 858-868, 1996.
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`Velculescu VE, Zhang L, Zhou W, Vogelstein J, Basrai MA, Bassett D Jr, Hieter P,
`Vogelstein B, Kinzler, KW. Characterization of the yeast transcriptome. Cell 88: 243-
`251, 1997.
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`Zhang L, Zhou W, Velculescu VE, Kern S, Hruban R, Hamilton S, Vogelstein B,
`Kinzler, KW. Gene expression profiles in normal and cancer cells. Science 276: 1268-
`1272, 1997.
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`Zhou W, Sokoll LJ, Bruzek DJ, Zhang L, Velculescu VE, Goldin SB, Hruban R, Kern
`SE, Hamilton SR, Chan DW, Vogelstein BV, Kinzler KW. Identifying markers for
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`pancreatic cancer by gene expression analysis. Cancer Epidemiology, Biomarkers and
`Prevention 7: 109-112, 1998.
`10. Bertelsen AH and Velculescu VE. High throughput gene expression analysis using
`SAGE. Drug Discovery Today 3: 152-160, 1998.
`11. Basrai, MA, Velculescu VE, Kinzler, KW, Hieter, P. NORF5/HUG1 couples DNA
`damage to checkpoint function. Molecular and Cellular Biology 19: 7041-7049, 1999.
`12. Lal A, Lash A, Altschul S, Velculescu VE, Zhang L, McLendon R, Marra M, Prange C,
`Morin P, Polyak K, Papadopoulos N, Vogelstein B, Kinzler K, Strausberg R, Riggins G.
`A Public Database for Gene Expression in Human Cancers. Cancer Research 59: 5403-
`7, 1999.
`13. Velculescu VE, Madden SL, Zhang L, Lash AE, Yu J, Rago C, Lal A, Wang CJ,
`Beaudry GA, Ciriello KM, Cook BP, Dufault MR, Ferguson AT, Gao Y, He TC,
`Hermeking H, Hiraldo SK, Hwang PM, Lopez MA, Luderer HF, Mathews B, Petroziello
`JM, Polyak K, Zawel L, Zhang W, Zhang X, Zhou W, Haluska FG, Jen J, Sukumar S,
`Landes GM, Riggins GJ, Vogelstein B, Kinzler KW. Analysis of human transcriptomes.
`Nature Genetics 23: 387-8, 1999.
`14. Velculescu VE. Tantalizing Transcriptomes – SAGE and its use in global gene
`expression analysis. Science 286: 1491-1492, 1999.
`15. St Croix B, Rago C, Velculescu VE, Traverso G, Romans KE, Montgomery E, Lal A,
`Riggins GJ, Lengauer C, Vogelstein B, Kinzler KW. Genes Expressed in Human Tumor
`Endothelium. Science 289: 1197-202, 2000.
`16. Velculescu VE, Vogelstein B, Kinzler KW. Analysing uncharted transcriptomes using
`SAGE. Trends in Genetics 16: 423-5, 2000.
`17. Howe JR, Bair JA, Sayed MG, Anderson ME, Mitros FA, Petersen GM, Velculescu VE,
`Traverso G, Vogelstein, B. Germline mutations of the gene encoding bone
`morphogenetic protein receptor 1A in juvenile polyposis. Nature Genetics 28:184-7,
`2001.
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`18.
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`Jones SJM, Riddle DL, Pouzyrev AT, Velculescu VE, Hillier L, Eddy SR, Stricklin SL,
`Baillie DL, Waterston R, Marra MA. Changes in Gene Expression Associated with
`Developmental Arrest and Longevity in Caenorhabditis elegans. Genome Research 11:
`1346-1352, 2001.
`19. Saha S, Bardelli A, Buckhaults P, Velculescu VE, Rago C, St Croix B, Romans KE,
`Choti MA, Lengauer C, Kinzler KW, Vogelstein B. A Phosphatase Associated with
`Metastasis of Colorectal Cancer. Science 294:1343-6, 2001.
`20. Wang TL, Rago C, Silliman N, Ptak J, Parmigiani G, Kinzler KW, Vogelstein B, and
`Velculescu VE. Prevalence of somatic alterations in the colorectal cancer genome.
`Proceedings of the National Academy of Sciences USA 99:3076-3080, 2002.
`21. Saha S, Sparks AB, Rago C, Akmaev V, Wang CJ, Vogelstein B, Kinzler KW,
`Velculescu VE. Using the transcriptome to annotate the genome. Nature Biotechnology
`20:508-12, 2002.
`22. Yan H, Yuan W, Velculescu VE, Vogelstein B and Kinzler KW. Allelic variation in
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`human gene expression. Science 297:1143, 2002.
`23. Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE.
`RAF/RAS oncogenes and mismatch-repair status. Nature 418:934, 2002.
`24. Wang TL, Maierhofer C, Speicher MR, Lengauer C, Vogelstein B, Kinzler KW,
`Velculescu VE. Digital Karyotyping. Proceedings of the National Academy of Sciences
`USA 99:16156-16161, 2002.
`25. Bardelli A, Parsons DW, Silliman N, Ptak J, Szabo S, Saha S, Markowitz S, Willson JK,
`Parmigiani G, Kinzler KW, Vogelstein B, Velculescu VE. Mutational analysis of the
`tyrosine kinome. Science 300:949, 2003.
`26. Buckhaults P, Zhang Z, Chen YC, Wang TL, St Croix B, Saha S, Bardelli A, Morin PJ,
`Polyak K, Hruban RH, Velculescu VE, Shih IeM. Identifying tumor origin using a gene
`expression-based classification map. Cancer Research 63(14):4144-9, 2003.
`27. Bardelli A, Saha S, Sager JA, Romans KE, Xin B, Markowitz SD, Lengauer C,
`Velculescu VE, Kinzler KW, Vogelstein B. PRL-3 expression in metastatic cancers.
`Clinical Cancer Research 9(15):5607-5615, 2003.
`28. Rajagopalan H, Jallepalli P, Rago C, Velculescu VE, Kinzler KW, Vogelstein B,
`Lengauer C. Inactivation of hCDC4 can cause chromosomal instability. Nature
`428(6978):77-81, 2004.
`29. Wang TL, Diaz LA, Romans K, Bardelli A, Saha S, Glizia G, Choti M, Donehower R,
`Parmigiani G, Shih I, Iacabuzio-Donahue C, Kinzler KW, Vogelstein B, Lengauer C,
`Velculescu VE. Digital karyotyping identifies thymidylate synthase amplification as a
`mechanism of resistance to 5-FU in metastatic colorectal cancer patients. Proceedings of
`the National Academy of Sciences USA 101(9):3089-94, 2004.
`30. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell
`SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE.
`High frequency of mutations of the PIK3CA gene in human cancers. Science 304(5670):
`554, 2004.
`31. Wang Z, Cummins JM, Shen D, Cahill DP, Jallepalli PV, Wang TL, Parsons DW,
`Traverso G, Awad M, Silliman N, Ptak J, Szabo S, Willson JK, Markowitz SD, Goldberg
`ML, Karess R, Kinzler KW, Vogelstein B, Velculescu VE and Lengauer C. Three
`classes of genes mutated in colorectal cancers with chromosomal instability. Cancer
`Research 64 (9): 2998-3001, 2004.
`32. Wang Z, Shen D, Parsons DW, Bardelli A, Sager J, Szabo S, Ptak J, Silliman N, Peters
`BA, Van Der Heijden MS, Parmigiani G, Yan H, Wang TL, Riggins G, Powell SM,
`Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE*. Mutational
`analysis of the tyrosine phosphatome in colorectal cancers. Science 304(5674):1164-6,
`2004.
`33. Broderick DK, Di C, Parrett TJ, Samuels YR, Cummins JM, Mclendon RE, Fults DW,
`Velculescu VE, Bigner DD, Yan Y. Mutations of PIK3CA in anaplastic
`oligodendrogliomas, high-grade astrocytomas and medulloblastomas. Cancer Research
`64(15):5048-50, 2004.
`
`PGDX EX. 1019
`Page 8 of 38
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`
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`VICTOR E. VELCULESCU, M.D., Ph.D.
`
`
`
`
`
`
`
`
`
`
`
`
`
`9
`
`34. Bachman KE, Argani P, Samuels Y, Silliman N, Ptak J, Szabo S, Konishi H, Karakas B,
`Blair BG, Lin C, Peters BA, Velculescu VE, and Park BH. The PIK3CA gene is
`mutated with high frequency in human breast cancers. Cancer Biology and Therapy 3:8,
`e49-e52.
`35. Samuels Y and Velculescu VE. Oncogenic mutations of PIK3CA in human cancers.
`Cell Cycle, 3 (10): 1221-1224, 2004.
`36. Bentires-Alj M, Paez JG, David FS, Keilhack H, Halmos B, Naoki K, Maris JM,
`Richardson A, Bardelli A, Sugarbaker DJ, Richards WG, Du J, Girard L, Minna JD, Loh
`ML, Fisher DE, Velculescu VE, Vogelstein B, Meyerson M, Sellers WR, Neel BG.
`Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human
`solid tumors and adult acute myelogenous leukemia. Cancer Research 64(24):8816-20,
`2004.
`37. Barber TD, Vogelstein B, Kinzler KW, Velculescu VE. Somatic mutations of EGFR in
`colorectal cancers and glioblastomas. New England Journal of Medicine 351(27):2883,
`2004.
`38. Bardelli A, Velculescu VE. Mutational analysis of gene families in human cancer. Curr
`Opin Genet Dev. 15(1):5-12, 2005.
`39. Di C, Liao S, Adamson DC, Parrett TJ, Broderick DK, Shi Q, Lengauer C, Cummins JM,
`Velculescu VE, Fults DW, McLendon RE, Bigner DD, Yan H. Identification of OTX2
`as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid.
`Cancer Research 65(3):919-24, 2005.
`40. Peters BA, Velculescu VE. Transcriptome PETs: A genome's best friends. Nature
`Methods 2, 93 – 94, 2005.
`41. Samuels Y, Diaz LA Jr, Schmidt-Kittler O, Cummins JM, Delong L, Cheong I, Rago C,
`Huso DL, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE. Mutant PIK3CA
`promotes cell growth and invasion of human cancer cells. Cancer Cell 7(6):561-73,
`2005.
`42. Hu M, Yao J, Cai L, Bachman KE, van den Brule F, Velculescu V, Polyak K. Distinct
`epigenetic changes in the stromal cells of breast cancers. Nature Genetics 37, 899-905,
`2005.
`43. Parsons DW, Wang TL, Samuels Y, Bardelli A, Cummins JM, DeLong L, Silliman N,
`Ptak J, Szabo S, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Lengauer C,
`Velculescu VE. Colorectal cancer: mutations in a signalling pathway. Nature
`436(7052):792, 2005.
`44. Cummins JM, He Y, Leary RJ, Pagliarini R, Diaz LA Jr, Sjöblom T, Barad O, Bentwich
`Z, Szafranska AE, Labourier E, Raymond CK, Roberts BS, Juhl H, Kinzler KW,
`Vogelstein B, Velculescu VE. The colorectal microRNAome. Proceedings of the
`National Academy of Sciences USA. 103(10):3687-92, 2006.
`45. Nakayama K, Nakayama N, Davidson B, Katabuchi H, Kurman RJ, Velculescu VE,
`Shih IM, Wang TL. Homozygous Deletion of MKK4 in Ovarian Serous Carcinoma.
`Cancer Biology & Therapy. 5(6):630-4, 2006.
`
`PGDX EX. 1019
`Page 9 of 38
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`
`
`
`
`
`
`
`
`
`
`
`
`
`10
`
`46. Nakayama K, Nakayama N, Kurman RJ, Cope L, Pohl G, Samuels Y, Velculescu VE,
`Wang TL, Shih IM. Sequence Mutations and Amplification of PIK3CA and AKT2
`Genes in Purified Ovarian Serous Neoplasms. Cancer Biology & Therapy. 26;5(7),
`2006.
`47. Wood LD, Calhoun ES, Silliman N, Ptak J, Szabo S, Powell SM, Riggins GJ, Wang TL,
`Yan H, Gazdar A, Kern SE, Pennacchio L, Kinzler KW, Vogelstein B, Velculescu VE.
`Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers. Human
`Mutation. 27(10):1060-1, 2006.
`48. Sjöblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber T, Mandelker D, Leary RJ,
`Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J,
`Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH,
`Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE. The
`Consensus Coding Sequences of Human Breast and Colorectal Cancers. Science.
`314(5797):268-74, 2006.
`49. Edkins S, O'meara S, Parker A, Stevens C, Reis M, Jones S, Greenman C, Davies H,
`Dalgliesh G, Forbes S, Hunter C, Smith R, Stephens P, Goldstraw P, Nicholson A, Chan
`TL, Velculescu VE, Yuen ST, Leung SY, Stratton MR, Futreal A. Recurrent KRAS
`Codon 146 Mutations in Human Colorectal Cancer. Cancer Biol Ther. 5(8):928-32,
`2006.
`50. Cummins JM, Velculescu VE. Implications of micro-RNA profiling for cancer
`diagnosis. Oncogene. 25(46):6220-7, 2006.
`51. Bettegowda C, Huang X, Lin J, Cheong I, Kohli M, Szabo SA, Zhang X, Diaz LA Jr,
`Velculescu VE, Parmigiani G, Kinzler KW, Vogelstein B, Zhou S. The genome and
`transcriptomes of the anti-tumor agent Clostridium novyi-NT. Nature Biotechnology.
`24(12):1573-1580, 2006.
`52. Peters BA, St Croix B, Sjöblom T, Cummins JM, Silliman N, Ptak J, Saha S, Kinzler
`KW, Hatzis C, Velculescu VE. Large-scale identification of novel transcripts in the
`human genome. Genome Research 17(3):287-92, 2007.
`53. Zhang X, Guo A, Yu J, Possemato A, Chen Y, Zheng W, Polakiewicz RD, Kinzler KW,
`Vogelstein B, Velculescu VE, Wang ZJ. Identification of STAT3 as a substrate of
`receptor protein tyrosine phosphatase T. Proc Natl Acad Sci U S A. 104(10):4060-4,
`2007.
`54. Velculescu VE, Kinzler KW. Gene expression analysis goes digital. Nature
`Biotechnology 25(8):878-80, 2007.
`55. Lin J, Gan CM, Zhang X, Jones S, Sjöblom T, Wood LD, Parsons DW, Papadopoulos N,
`Kinzler KW, Vogelstein B, Parmigiani G, Velculescu VE. A multidimensional analysis
`of genes mutated in breast and colorectal cancers. Genome Research 17 (9):1304-18,
`2007.
`56. Leary RJ, Cummins J, Wang TL, Velculescu VE. Digital karyotyping. Nature
`Protocols. 2(8):1973-86, 2007.
`57. Rago C, Huso DL, Diehl F, Karim B, Liu G, Papadopoulos N, Samuels Y, Velculescu
`
`PGDX EX. 1019
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`VICTOR E. VELCULESCU, M.D., Ph.D.
`
`
`
`
`
`
`
`
`
`
`
`
`
`11
`
`VE, Vogelstein B, Kinzler KW, Diaz LA Jr. Serial assessment of human tumor burdens
`in mice by the analysis of circulating DNA. Cancer Res. 67(19):9364-70, 2007.
`58. Wood LD, Parsons DW, Jones S, Lin J, Sjöblom T, Leary RJ, Shen D, Boca SM, Barber
`T, Ptak J, Silliman N, Szabo S, Dezso Z, Ustyanksky V, Nikolskaya T, Nikolsky Y,
`Karchin R, Wilson PA, Kaminker JS, Zhang Z, Croshaw R, Willis J, Dawson D,
`Shipitsin M, Willson JK, Sukumar S, Polyak K, Park BH, Pethiyagoda CL, Pant PV,
`Ballinger DG, Sparks AB, Hartigan J, Smith DR, Suh E, Papadopoulos N, Buckhaults P,
`Markowitz SD, Parmigiani G, Kinzler KW*, Velculescu VE*, Vogelstein B*. The
`Genomic Landscapes of Human Breast and Colorectal Cancers. Science.
`318(5853):1108-13, 2007. *corresponding author
`59. Beerenwinkel N, Antal T, Dingli D, Traulsen A, Kinzler KW, Velculescu VE,
`Vogelstein B, Nowak MA. Genetic progression and the waiting time to cancer. PLoS
`Comput Biol. 3(11):e225, 2007.
`60. Huang CH, Mandelker D, Schmidt-Kittler O, Samuels Y, Velculescu VE, Kinzler KW,
`Vogelstein B, Gabelli SB, Amzel LM. The structure of a human p110alpha/p85alpha
`complex elucidates the effects of oncogenic PI3Kalpha mutations. Science.
`318(5857):1744-8, 2007.
`61. Segal NH, Parsons DW, Peggs KS, Velculescu V, Kinzler KW, Vogelstein B, Allison
`JP. Epitope landscape in breast and colorectal cancer. Cancer Res. 68(3):889-92, 2008.
`62. Barber TD, McManus K, Yuen KW, Reis M, Parmigiani G, Shen D, Barrett I, Nouhi Y,
`Spencer F, Markowitz S, Velculescu VE, Kinzler KW, Vogelstein B, Lengauer C, Hieter
`P. Chromatid cohesion defects may underlie chromosome instability in human colorectal
`cancers. Proc Natl Acad Sci U S A. 105:3443-48, 2008. PMCID: PMC2265152.
`
`63.
`
`Jones S, Chen WD, Parmigiani G, Diehl F, Beerenwinkel N, Antal T, Traulsen A,
`Nowak MA, Siegel C, Velculescu VE, Kinzler KW, Vogelstein B, Willis J, Markowitz
`SD. Comparative lesion sequencing provides insights into tumor evolution. Proc Natl
`Acad Sci U S A. 105(11):4283-8, 2008. PMCID: PMC2393770.
`64. Picelli S, Vandrovcova J, Jones S, Djureinovic T, Skoglund J, Zhou XL, Velculescu VE,
`Vogelstein B, Lindblom A. Genome-wide linkage scan for colorectal cancer
`susceptibility genes supports linkage to chromosome 3q. BMC Cancer. 8:87, 2008.
`PMCID: PMC2324103.
`65. Velculescu VE. Defining the blueprint of the cancer genome. Carcinogenesis.
`29(6):1087-91, 2008. PMCID: PMC2825145.
`66. Chan TA, Glockner S, Yi JM, Chen W, Van Neste L, Cope L, Herman JG, Velculescu
`V, Schuebel KE, Ahuja N, Baylin SB. Convergence of mutation and epigenetic
`alterations identifies common genes in cancer that predict for poor prognosis. PLoS
`Med. 5(5):e114, 2008. PMCID: PMC2429944.
`67. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H,
`Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky
`Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK,
`Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G,
`Vogelstein B*, Velculescu VE*, Kinzler KW*