The Cancer genome atlas TCGA and the search for a CUP geneticepigenetic signature Manel Esteller MD PhD Director Josep Carreras Leukaemia Research Institute IJC Director Cancer Epigenetics and Biology Program PEBC ID: 772073
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The Cancer genome atlas (TCGA) and the search for a CUP genetic/epigenetic signatureManel Esteller, MD, PhD.Director, Josep Carreras Leukaemia Research Institute (IJC)Director, Cancer Epigenetics and Biology Program (PEBC)ICREA Research ProfessorGenetics Chairman, School of Medicine, University of Barcelona
35participating institutions>150collaborators 47 paired CUP cases (N&T) Goal n=500 2 years Sept 2018– Sept 2020 TCGA CUP project
Cost to NCI is approximately:Tissue Acquisition: $500 per case, for a total of $250,000Tissue Processing: $2000/per case, for a total cost of $1,000,000.Tissue Characterization: $5000/case, for a total of 2,500,000Total Investment: $3,750,000$ Project budget
TCGA CUP projectClinicaldataGenomicEpigenomicTrans-criptomic Collate 500 paired CUP/normal samples with comprehensive clinical information to perform a multi- omic characterization Genomic Epigenomic Transcriptomic
Collaborators from America*samples are submitted directly to NCHMTA must be established between your institution and the Nationwide Children’s Hospital (NCH) at USA.Collaborators outside AmericaThe NCH does not require to sign a MTA with collaborator institutions that do not are sending samples directly to NCH. However, if your institution requires to establish an agreement or contract, our institution (IJC) will be glad to sign it.Material Transfer and Data Use Agreements
1 2 3 4 15 TGCA CUPP collaborator institutions
Collaborator Hospitals & Institutionsaround the world + Normal Tumor Clinical data PROSPECTIVE & RETROSPECTIVE SAMPLES (RS) PROSPECTIVE SAMPLES Frozen blood (8-10 ml, EDTA tube ) Frozen tissue (50 mg) FFPE block LAST OPTION * express shipping * risk of degradation FFPE sections (10-20 sections , 10 um ) FFPE block (normal tissue ) FFPE sections (10-20 sections , 10 um ) Are you interested in becoming part of this multicentric world-wide TCGA project , providing CUP samples ?
TGCA CUPP OUTCOMEExpand our knowledge about the molecular mechanisms governing CUP development.Define the existence of different entities, now grouped as CUPs.Identify potential therapeutic targets that can be translated to the clinical practice.
Duruisseaux et al., The Lancet Respiratory Medicine 2018 Genome-wide DNA methylation profile: Illumina 850k array beadchip Methylation level in each CpG explored Pre-anti-PD1 FFPE samples from NSCLC Fully clinically annotated DNA extraction >250 ng Bioinformatic
EPIMMUNE Positive NSCLC : Prediction of Response to Anti-PD1 Therapy At risk : EPIMMUNE 10 10 10 10 8 7 + 24 11 7 5 5 5 - At risk : EPIMMUNE 10 10 7 5 4 4 + 24 1 0 0 0 0 - A Log- rank ; P < 10 -6 HR (95%CI)= 0.010 (3.29x 10 -4 – 0.0282); P=0.007 EPIMMUNE + (N=10) EPIMMUNE – (N=24) Log- rank ; P < 10 -3 HR (95%CI)= 0.080 ( 0.017 – 0.373); P=0.001 EPIMMUNE – (N=24) EPIMMUNE + (N=10) Log- rank ; P= 0.004 HR (95%CI)= 0.330 (0.149 – 0.727); P=0.006 EPIMMUNE – (N=33) EPIMMUNE + (N=14) At risk : EPIMMUNE 14 6 6 6 6 + 33 6 2 0 0 - B PD-L1 positive CD8 high Mutational Load Duruisseaux et al. The Lancet Respiratory Medicine 2018
Log-rank; P< 10-5HR (95%CI)= 0.124 (0.043 - 0.356);P<0.001 NSCLC Discovery Cohort (N=34)EPIMMUNE-TCGA signature EPIMMUNE – (N=22) EPIMMUNE + (N=12) A At risk : EPIMMUNE 12 10 7 5 4 4 + 22 1 0 0 0 0 - Log- rank ; P=0.019 HR (95%CI)= 0.293 (0.100 – 0.863);P=0.026 EPIMMUNE – (N=22) EPIMMUNE + (N=12) At risk : EPIMMUNE 12 10 9 9 7 6 + 22 11 6 6 6 6 - NSCLC Discovery Cohort (N=34) EPIMMUNE-TCGA signature B Log- rank ; P=0.927 HR (95%CI)= 0.989 (0.587 – 1.665);P=0.967 TCGA NSCLC cohorts (N=582) EPIMMUNE - TCGA signature EPIMMUNE – (N=472) EPIMMUNE + (N=110) At risk : EPIMMUNE 110 74 71 70 70 + 472 300 282 280 279 - EPIMMUNE-TCGA Positive NSCLC : Prediction of Response to Anti- PD1 Therapy Duruisseaux et al. The Lancet Respiratory Medicine 2018
DNA Methylation Profiling Could Predict Clinical Response to PD1 Blockade in CUP-NSCLC
BENEFITS FOR COLLABORATORSAccess to multi-omic data for CUP cases.Authorship in top high-impact publications (i.e. Nature, Science, Cell…)
mesteller@carrerasresearch.org