1 / 15

The Cancer genome atlas (TCGA) and the search for a CUP genetic/epigenetic signature

The Cancer genome atlas (TCGA) and the search for a CUP genetic/epigenetic signature Manel Esteller , MD, PhD. Director, Josep Carreras Leukaemia Research Institute (IJC) Director, Cancer Epigenetics and Biology Program (PEBC) ICREA Research Professor

juanitac
Download Presentation

The Cancer genome atlas (TCGA) and the search for a CUP genetic/epigenetic signature

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. The Cancer genome atlas (TCGA) and the search for a CUP genetic/epigenetic signature ManelEsteller, MD, PhD. Director, Josep Carreras Leukaemia Research Institute (IJC) Director, Cancer Epigenetics and Biology Program (PEBC) ICREA Research Professor Genetics Chairman, School of Medicine, University of Barcelona

  2. TCGA CUP project 2 years Sept 2018– Sept 2020 35 participating institutions >150 collaborators 47 Goal n=500 paired CUP cases (N&T)

  3. Project budget Cost to NCI is approximately: Tissue Acquisition: $500 per case, for a total of $250,000 Tissue Processing: $2000/per case, for a total cost of $1,000,000. Tissue Characterization: $5000/case, for a total of 2,500,000 Total Investment: $3,750,000$

  4. TCGA CUP project • Collate 500 paired CUP/normal samples with comprehensive clinical information to perform • a multi-omic characterization • Genomic • Epigenomic • Transcriptomic Epi genomic Genomic Clinical data Trans- criptomic

  5. Material Transfer and Data Use Agreements Collaborators from America *samples are submitted directly to NCH MTA must be established between your institution and the Nationwide Children’s Hospital (NCH) at USA. Collaborators outside America The 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.

  6. TGCA CUPP collaborator institutions 1 2 3 4 15

  7. Are youinterested in becomingpart of thismulticentricworld-wide TCGA project, providing CUP samples? Collaborator Hospitals & Institutions aroundtheworld • Tumor FFPE sections (10-20 sections, 10 um) Frozentissue (50 mg) FFPE block Clinical data + • Normal Frozenblood (8-10 ml, EDTA tube) FFPE sections (10-20 sections, 10 um) FFPE block (normal tissue) PROSPECTIVE & RETROSPECTIVE SAMPLES (RS) PROSPECTIVE SAMPLES LAST OPTION *expressshipping *risk of degradation

  8. TGCA CUPP OUTCOME • Expand 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.

  9. DNA extraction >250 ng Bioinformatic Pre-anti-PD1 FFPE samplesfromNSCLCFullyclinicallyannotated Methylationlevel in eachCpGexplored Genome-wide DNA methylation profile: Illumina 850k array beadchip Duruisseaux et al., The Lancet Respiratory Medicine 2018

  10. EPIMMUNE Positive NSCLC : Prediction of Response to Anti-PD1 Therapy A EPIMMUNE + (N=10) EPIMMUNE + (N=10) EPIMMUNE – (N=24) EPIMMUNE – (N=24) Log-rank; P < 10-3 HR (95%CI)= 0.080 (0.017 – 0.373); P=0.001 Log-rank; P < 10-6 HR (95%CI)= 0.010 (3.29x10-4 – 0.0282); P=0.007 B PD-L1 positive CD8 high Log-rank; P= 0.004 HR (95%CI)= 0.330 (0.149 – 0.727); P=0.006 EPIMMUNE + (N=14) Mutational Load EPIMMUNE – (N=33) Duruisseaux et al. The Lancet Respiratory Medicine 2018

  11. EPIMMUNE-TCGA Positive NSCLC : Prediction of Response to Anti-PD1 Therapy A B NSCLC DiscoveryCohort (N=34) EPIMMUNE-TCGAsignature TCGA NSCLC cohorts (N=582) EPIMMUNE -TCGAsignature NSCLC DiscoveryCohort (N=34) EPIMMUNE-TCGAsignature Log-rank; P<10-5 HR (95%CI)= 0.124 (0.043 - 0.356);P<0.001 Log-rank; P=0.927 HR (95%CI)= 0.989 (0.587 – 1.665);P=0.967 EPIMMUNE + (N=12) EPIMMUNE + (N=110) Log-rank; P=0.019 HR (95%CI)= 0.293 (0.100 – 0.863);P=0.026 EPIMMUNE – (N=22) EPIMMUNE – (N=472) EPIMMUNE + (N=12) EPIMMUNE – (N=22) Duruisseaux et al. The Lancet Respiratory Medicine 2018

  12. DNA Methylation Profiling Could Predict Clinical Response to PD1 Blockade in CUP-NSCLC

  13. BENEFITS FOR COLLABORATORS • Access to multi-omic data for CUP cases. • Authorship in top high-impact publications (i.e. Nature, Science, Cell…)

  14. mesteller@carrerasresearch.org

More Related