1st International Symposium of MEXT Program“Fostering Health Professionals for Changing
Needs of Cancer”

Genomic Medicine
Kanto Academic Alliance for Fostering
Cancer Professionals

February 17, Sat 10:0017:00
ROSE HALL(Maebashi Chamber of Commerce and Industry)PROGRAM
Welcome address
10:3010:35

Prof. Yasuki ISHIZAKI(Dean, Gunma University Graduate School of Medicine)

Session I. Cancer Genomic Medicine
Moderator: Hisahiro MATSUBARA(Graduate School of Medicine, Chiba University)
10:35 ~ 11:15
Implementation of “Clinical Sequencing” in Cancer Genome Medicine inJapan
Dr. Takashi KOHNO(Division of Genome Biology, National Cancer Center Research Institute/ Division ofTranslational Research, Exploratory Oncology Research & Clinical Trial Center (EPOC),
National Cancer Center, JPN)

11:15 ~ 11:50
Genome Sequencing Analysis for Cancer Research and Precision Medicine
Dr. Hidewaki NAKAGAWA(Laboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical
Sciences, JPN)

11:50 ~ 12:50

Lunch

Session. Toward Further ProgressOmics Analysis and Bioinformatics
Moderator: Prof. Masahiko NISHIYAMA(Gunma university Graduate School of Medicine)

12:50 ~ 13:30
Identification of Novel Therapeutic Targets for Cancer Based on the Omics
Cancer-Assciated Fibroblasts: Tumor Allies and Foes
Dr. Andrei TURTOI(Tumor Microenvironment and Resistance to Treatment, Institute of Cancer Research ofMontpellier, FRA)

13:30 ~ 14:10
Innovative strategies to identify and validate new OMICs biomarkers withhigh translational potential for diagnostic, prognostic and treatment inoncology
Prof. Vincent CASTRONOVO(Laboratory of Metastases Research, GIGA-CANCER, Liege University, BEL)

14:10 ~ 14:50
The dynamic cerebrospinal fluid proteome and a perspective on a new classof biomarkers
Prof. Jacques COLINGE(Cancer Bioinformatics and System Biology, , Institute of Cancer Research of Montpellier, FRA)

14:50 ~ 15:00

Coffee Break

Guidance Session for Students : Meet the Experts
15:00 ~ 16:55
Student attendance will be separated into 5 groups and rotate 5 stations to
directly ask something to 5 invited speakers in order to be a specialist of Cancer
Genomic Medicine. Each invited speakers will give advices and supervise to
students from a view point of each special field.
Closing Remarks
16:5517:00

Prof. Nobuhiro OHKOHCHI(Project Director/ Graduate School of Comprehensive Human

Science,
University of Tsukuba)

Takashi Kohno, Ph.D

Position: Chief, Division of Genome Biology, Research InstituteChief, Division of Translational Genomics, Exploratory Oncology
Research and Clinical Trial Center (EPOC)
National Cancer Center, Japan

Address: 5-1-1, Tsukiji, Chuo-ku, Tokyo 1040045, JapanTEL:+81-3-3547-5272
E-mail: tkkohno@ncc.go.jp
EDUCATION
Kyoto University, School of Pharmacy, Kyoto, Japan (1985-1989)
Kyoto University, Graduate School of Pharmacy, Kyoto, Japan (1989-1991)
Tokyo University, Graduate School of Medicine, Tokyo, Japan (1991-1995)

WORK EXPERIENCE
Researcher, Biology Division (Dr. Yokota Lab)
National Cancer Center Research Institute (1995-2000)
Section Head, Biology Division (Dr. Yokota Lab)
National Cancer Center Research Institute (2000-2010)
Chief, Division of Genome Biology
National Cancer Center Research Institute (2011-present)
Chief, Division of Translational Genomics
EPOC, National Cancer Center (2013-present)

CERTIFICATION
Doctor of Philosophy, Tokyo University (1995)

RESEARCH INTEREST

Cancer genome medicine

Dr. Takashi Kohno is currently a Chief in Division of Genome Biology of National Cancer
Center Research Institute, Japan. Dr. Kohno graduated from Kyoto University in 1989. Hereceived PhD from Tokyo University. From 1995, he has studied lung cancer genetics andgenomics in National Cancer Center. His representative research product is the finding of
RET fusion in lung adenocarcinoma and its translation to lung cancer clinic. He is also a
Chief of Division of Translational Research, Exploratory Oncology Research and Clinical
Trial Center, National Cancer Center Research Institute. His research area includes
genomics, genetics (polymorphisms), and cancer genome medicine.

Implementation of “Clinical Sequencing” in Cancer Genome
Medicine in Japan
Takashi Kohno
Division of Genome Biology, National Cancer Center Research Institute
Division of Translational Genomics, Exploratory Oncology Research and Clinical Trial
Center, National Cancer CenterIn oncology, actionable mutations (alterations) in cancer-associated genes are
critical in terms of the selection of therapeutic approaches. Next-generation
sequencing (NGS) of tumor sample DNA (i.e., clinical sequencing) can guide clinicalmanagement by providing diagnostic or prognostic data, and facilitating theidentification of potential treatment regimens, such as molecular-targeted andimmune checkpoint blockade therapies. In the U.S., a variety of multi-gene panels
have been developed and implemented for this purpose. In Japan, several academic
institutions have now performed detailed investigations of the feasibility and valueof clinical sequencing, and cancer societies have issued consensus clinical practiceguidelines for NGS-based tests. These efforts will facilitate the implementation ofcancer genome medicine in Japan.
1) Kohno T et al. KIF5B-RET fusions in lung adenocarcinoma. Nat Med, 2012.
2) Yoh K et al. Vandetanib in patients with previously treated RET-rearranged advanced nonsmall-cell lung cancer (LURET): an open-label, multicentre phase 2 trial. Lancet Respir Med,
2017.
3) Tanabe et al. Comprehensive screening of target molecules by next-generation sequencing
in patients with malignant solid tumors: guiding entry into phase I clinical trials. Mol
Cancer, 2016.
3) Kohno T. Implementation of "Clinical Sequencing" in cancer genome medicine inJapan. Cancer Sci, 2018, in press.

Hidewaki Nakagawa, MD, PhD

1991

Osaka University, School of Medicine (M.D.)

1991

Osaka University Hospital, General Surgery, Resident

1992

Osaka University Hospital, ICU/ Anesthesiology, Resident

1993

National Osaka Hospital, GI surgery and breast surgey, Resident

1996

Osaka University, Graduate School of Medicine (Ph.D. 2000)

1999

The Ohio State University, Human Cancer Genetics Program,
Postdoctoral fellow

2003

Assitant Professor / Associate Professor, Human Genome Center, Institute ofMedical Science, The University of Tokyo

2008

Laboratory Head, Laboratory for Biomarker Development, RIKEN Center for
Genomic Medicine

2013 -

Laboratory Head, Laboratory for Genome Sequencing Analysis, RIKEN Center
for Integrative Medical Sciences

2015 -

Program Officer of Biobank/Genomic Medicine project in AMED

Dr. Hidewaki Nakagawa graduated from Osaka University School of Medicine in 1991, andhe completed training in clinical oncology of GI & breast cancers and critical care medicine
as a surgeon. He obtained his PhD in 2000 from Osaka University for genomic research ofhereditary colon cancer. After four years postdoctoral training of colon cancer genomics atthe Human Cancer Genetics Program, The Ohio State University, USA, he returned to Japanas an assistant/associate professor at Institute of Medical Science, The University of Tokyo,
where he was dedicated to therapeutic target screening for pancreatic and prostate cancers.
In 2008, he moved to RIKEN as a team leader of genomic medicine. His recent research
focuses on cancer genomics by whole genome sequencing and cancer biomarker
development using next-generation sequencing. He has been working for cancer genome
sequencing analysis of liver cancer and GI cancers as one of the PIs of ICGC /TCGA

project. His main interest is genome-based personalized medicine and cancer
patient care.

Genome Sequencing Analysis for Cancer Research and Precision
Medicine
Hidewaki Nakagawa
RIKEN Center for Integrative Medical Sciences

Cancer is essentially a “disease of the genome” which develops and evolves with theaccumulation of a variety of mutations in the background of germline variants, andsome driver mutations such as EGFR, HER2, and BRCA1/2 were successfullytargeted for treatment. Explosive advances of next-generation sequencer (NGS) andcomputational analyses handling massive data enable us to comprehensively
analyze cancer genome profiles in research and clinical levels, such as targeted
sequencing for hundreds of genes, whole exome sequencing (WES), RNA sequencing(RNA-Seq), and eventually whole genome sequencing (WGS) or cell-free DNA
sequencing. These approaches combined with mathematical analysis and other omics analysis can clarify the underlying carcinogenesis and cancer immunology
and achieve molecular sub-classification of cancer, which facilitates discovery ofgenomic biomarkers and personalized cancer medicine. I present recent technicalapproaches for cancer genome sequencing and the future direction of cancer
genome sequencing, and discuss its utility and limitation of an analysis platform andmutation interpretation for cancer genomics and cancer precision medicine.

Dr. Turtoi Andrei
Team Leader“Tumor Microenvironment and Resistance to Treatment”
Institut de Recherche en Cancérologie de Montpellier/Inserm U1194, Montpellier, France

EDUCATION
01.04.2008
2004
2003
1999

PhD (Faculty of Biology/ Department of Genetics, Technical University
Dresden, Germany.)
Dipl. Ing. (Faculty of Chemical Engineering/ University of Applied Sciences,
Aachen, Germany.)
B.Eng. (Faculty of Chemical Engineering/ University of Applied Sciences,
Aachen, Germany.)
International Baccalaureate (IB) (United World Colleges, Pune, India.)

PREVIOUS POSITIONS
07.2016 –09.20162015 – 201605.2015 –09.20152012 – 20152009 – 20122008 – 20092005 – 20082003 – 2004

Invited Lecturer (Assistant Professor)
Department of Molecular Pharmacology and Oncology,
Graduate School of Medicine, University of Gunma, Maebashi, Japan.
FNRS Scientific Collaborator (Televie Fellowship)
Faculty of Medicine/ GIGA-Cancer, Metastasis Research Laboratory,
University of Liege, Liege, Belgium.
Invited Lecturer (Assistant Professor)
Department of Molecular Pharmacology and Oncology,
Graduate School of Medicine, University of Gunma, Maebashi, Japan.
FNRS Charge de Recherché
Faculty of Medicine/ GIGA-Cancer, Metastasis Research Laboratory,
University of Liege, Liege, Belgium.
Principal Investigator
Faculty of Medicine/ GIGA-Cancer, Metastasis Research Laboratory,
University of Liege, Liege, Belgium.
Post Doctoral Fellow
Faculty of Sciences/ Department of Chemistry, Mass Spectrometry Laboratory,
University of Liege, Liege, Belgium.
PhD Fellow
Institute of Medicine, Laboratory of Radiation Biology, Forschungszentrum Jülich,
Germany.
Research Fellow
Department of Marine Chemistry, Alfred Wegener Institute for Polar and Marine
Research, Bremerhaven, Germany.

Cancer-Assciated Fibroblasts: Tumor Allies and Foes
Andrei Turtoi
Institut du Cancer Montpellier, Montpellier 34090, France;
INSERM U1194, Montpellier 34090, France;
Institut de Recherche en Cancérologie de Montpellier, Montpellier 34090, France;
Université Montpellier, Montpellier 34298, France;

Cancer associated fibroblasts are the major component of the tumor microenvironment& a rich source of growth factors, pro-angiogenic molecules and matrix proteins. In
contrast to for example macrophages, CAF are almost exclusively regarded as protumorigenic elements and as such they have been proposed as eligible tumor targets.
Unfortunately, CAF-directed targeted therapies have thus far not produced the desired
anti-tumor effects. These have either showed only modest tumor control or,
surprisingly, have induced tumoral progression. Emerging evidence suggest that oursimplistic picture of CAF is not correct and that these cells may also have intrinsic
tumor-defensive properties. Future studies of tumor microenvironment and notably
CAF will thus inevitably relay on single cell approaches, enabling a context andspatially-dependent observation of this highly heterogeneous cell population. In thepresent talk I will touch upon past and present works supporting such differentiatedpicture of CAF as well as present some newest research data from our lab.

Vincenzo CASTRONOVO
Professor
Faculty of Medicine, University of Liège

Work address: University of Liège - Metastases Research Laboratory
Tour de Pathologie, +4, Bât. B23 - B-4000 Liège
Tél. : +32 (0) 4 366 2479 - e-mail : vcastronovo@ulg.ac.be

Education
Medical Doctor, Surgery and obstetrics, University of Liège, 1983 – Summa Cum Laude.
PhD in biomedical sciences, University of Liège, 1987 – Summa Cum Laude.
Agrégé de l’Enseignement Supérieur, University of Liège, 1992 – Summa Cum Laude.
Board-Certified in Obstetrics and Gynecology, University of Liège, 1993 – Summa Cum
Laude.

University career
Head of Metastases Research Laboratory, University of Liège (Since 1992).
Supervisor of Gynecologics-Obstetrical Department. University of Liège (1993-1998).
Maître de Conférences. University of Liège (1994-1998).
Founder and director of the MetastasesResearch Laboratory (1992-to date)Maître de Recherches (Fonds National de la Recherche Scientifique (1994-1998).
Medical Director of the Centre Anti-Cancer. (1995-2003).
Director of the Center of Experimental Cancer Research (CRCE). University of Liège (20022007).
Professor (Full time). Faculty of Medicine, University of Liège (2005-2010).
Head of GIGA-Cancer. University of Liège (2008-2011).
Full Professor (Biology). Faculty of Medicine, University of Liège (Since 2011).
Member of the Royal Belgian Academy of Medicine.

Innovative strategies to identify and validate new OMICs
biomarkers with high translational potential for diagnostic,
prognostic and treatment in oncology
Vincent Castronovo1, Andrei Turtoi1,Brunella Costanza1 and Masahiko Nishiyama2
Metastasis Research Laboratory, GIGA Cancer, University of Liège, Liège, Belgium
Department of Molecular Pharmacology and Oncology,
Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
Biomarker discovery is a crucial step for cancer early diagnosis, prognosis,
prediction of therapy response and specific effective targeted therapies, particularlyin the field of oncology. The discovery of biomarkers that are readily accessible
through the circulating blood and are selectively overexpressed in pathologicaltissues has become a major research objective. This group of molecules has a highpotential to serve as a tool for imaging and targeted cancer therapy approaches. In
this therapeutic concept, specific cancer proteins are reached by intravenously
administered ligands that are coupled to cytotoxic drugs, able to induce cancer
destruction while sparing normal tissues. Current high-throughput proteomic
analysis allows for the identification of a high number of proteins that are
differentially expressed in the cancerous tissues. However, such approaches provide
no information regarding the accessibility of the biomarkers and, therefore, thepossibility for these discovered proteins to be targeted. To bypass this limitation,
which clearly slows the discovery of such biomarkers, we have developed, appliedand validated innovative technologies to efficiently identify accessible antigens
from clinically relevant samples. Another challenge in the biomarker field is theidentification of diagnostic and prognostic biomarkers from early lesions,
measurable in liquid biopsies. Fresh human material of high quality is required forbiomarker discovery but is often not available when it is totally required for clinicalpathology investigation. Hence, all OMICs studies are done on residual and lessclinically relevant biological samples. We have developed an innovative, simple, andnon-destructive, procedure named EXPEL that uses rapid, pressure-assisted,interstitial fluid extrusion, preserving the specimen for full routine clinicalpathology investigation. In the meantime, the technique allows a comprehensive
OMICs analysis (proteins, metabolites, miRNAs and DNA). As proof of concept, wehave applied EXPEL on freshly collected human colorectal cancer and liver
metastases tissues. We demonstrate that the procedure efficiently allows theextraction, within a few minutes, of a wide variety of biomolecules holding
diagnostic and prognostic potential while keeping both tissue morphology andantigenicity unaltered. Our method enables, for the first time, both clinicians andscientists to explore identical clinical material regardless of its origin and size, which
has a major positive impact on translation to the clinic. Our technology opens a new
era for biomarkers discovery and will have a major impact on translational research.
We trust that this method meets the emerging concept of precision medicine where
cancer diagnosis and treatment are tailored to the individual patient characteristics.

Jacques Colinge, PhD,
Professor
IRCM, ICM, and Faculty of Medicine University of Montpellier
Montpellier, France

Research Career
Ph.D. in Mathematics, University of Geneva, Switzerland
1998-2000
Bioinformatician & Scientist I, Serono Pharmaceutical Research Institute,
Geneva2000-2005
Head of Mass Spectrometry Bioinformatics and Parallel Computing, GeneProt
Inc., Geneva
2005-2006
Professor of Bioinformatics, Upper Austria University of Applied Sciences
2006-2014
Head of Bioinformatics, CeMM, Vienna, Austria
2009Habilitation & Adjunct Professor in Bioinformatics, Technische Universität
Graz
2014Full Professor University of Montpellier & Team Leader at IRCM
2014Adjunct PI, CeMM, Vienna

Research Interests
Systems and network biology method development applied to cancer and immunology
Personalized cancer therapy
Computational proteomics

The dynamic cerebrospinal fluid proteome and a perspective on a
new class of biomarkers
Jérôme Vialaret1, Christophe Hirtz1, Maxence Ory2,
Guillaume Gras Combe3, Luc Bauchet3, Marine Girard1, Audrey Gabelle1,4,
Sylvain Lehmann1, Jacques Colinge2,5
1CHRU de Montpellier, Université de Montpellier and INSERM U1183, IRMB, Laboratoire deBiochimie Protéomique Clinique, Montpellier, France
2IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Montpellier,France3Service de Neurochirurgie, CHRU de Montpellier, hôpital Gui de Chauliac, Montpellier, INSERM
U 1051 and Université de Montpellier, Montpellier, France
4Centre Mémoire de Ressources et de Recherche Languedoc-Roussillon, Département deNeurologie, CHRU de Montpellier, hôpital Gui de Chauliac, Montpellier, France
5ICM, Institut du Cancer de Montpellier, Montpellier, France

Intravenous administration of stable isotope labeled amino acid (13C6-leucine) tohumans recently made it possible to study the metabolism of specific biomarkers in
cerebrospinal fluid (CSF) using targeted mass spectrometry (MS). We have applied an
unbiased, large-scale approach to obtain hundreds of leucine-containing peptides inparallel using high-resolution MS. Advanced signal processing and mathematicalmodeling techniques allowed us to determine the rates of synthesis and clearance ofmore than 200 proteins in the CSF. Large-scale measures obtained from one individual
have been confirmed by targeted measures for a dozen of proteins in 4 patients.
These unpublished results pave the way to the study of proteome dynamics to unravel
novel biomarkers witnessing metabolic differences, abnormal protein turnover orderegulated fluxes between biological compartments, e.g. CSF and blood, in diseases. Our
results demonstrate that this new field of proteomic investigation can be conducted inhuman patients and biological fluids but the technique is obviously applicable to animalmodels and solid tissues with adaptations.

Gunma University Graduate
School of Medicine
Kanto Academic Alliance for Fostering
Cancer Professionals
MEXT Program “Fostering Health Professionals
for Changing Needs of Cancer”