1 / 23

GENOMIC ANALYSIS OF OVER 400 SARCOMAS

GENOMIC ANALYSIS OF OVER 400 SARCOMAS. – Gregory M. Cote – J. Butrynski, J. Shen, J. Morgan, Z. Duan, D. D’Adamo, G. Nielsen, S. George, F. Hornicek, G. Demetri, D. Harmon, C. Raut, J. Hornick, E. Choy, A. Wagner. No Disclosures. Objective:.

mala
Download Presentation

GENOMIC ANALYSIS OF OVER 400 SARCOMAS

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. GENOMIC ANALYSIS OF OVER 400 SARCOMAS – Gregory M. Cote – J. Butrynski, J. Shen, J. Morgan, Z. Duan, D. D’Adamo, G. Nielsen, S. George, F. Hornicek, G. Demetri, D. Harmon, C. Raut, J. Hornick, E. Choy, A. Wagner

  2. No Disclosures

  3. Objective: To identify the frequency and types of genomic alterations in sarcomas • Allele-specific mutation analysis (Profile) • Targeted exome sequencing (FoundationOne)

  4. Profile Mass spectrometry-based mutation hotspot analysis 471 mutations in 41 cancer-related genes Data collected prospectively Research study (internal DFCI funding) Methods

  5. Methods Profile Mass spectrometry-based mutation hotspot analysis 471 mutations in 41 cancer-related genes Data collected prospectively Research study (internal DFCI funding) FoundationOne Next-generation sequencing platform 3,769 exons in 236 genes and 47 introns from 19 genes commonly rearranged Data collected retrospectively Clinical study billed to insurance/patients

  6. Profile 377 Patient Samples

  7. Profile 377 Patient Samples • 74 mutations • 20% • - 9% (excluding GIST • and Desmoid)

  8. Profile 83 mutations in 74 of 377 (20%) patient samples

  9. 83 mutations in 74 of 377 (20%) patient samples Profile

  10. Targeted Exome Sequencing(3,769 exons in 236 genes and 47 introns from 19 genes commonly rearranged) 71 patient samples from clinic

  11. 162 DNA alterations 80% with >/= 1 Median = 2 (range 0-8)

  12. Cell Cycle 56 (52%) PI3K/Akt 16 (17%) Receptor Tyrosine Kinase (Amplifications) 19 (13%) MAPK 9 (13%) Epigenetic 21 (20%) DNA repair 6 (8%) Other 31 (38%) 162 DNA alterations

  13. Cell Cycle p15, p16 CDK4/6-Cyclin D CDK2-Cyclin E Rb M G1 MDM2 p53 G2 S

  14. p15, p16 15 (21%) CDK4/6-Cyclin D CDK2-Cyclin E 31 (44%) 8 (11%) Rb 8 (11%) M G1 12 (17%) MDM2 p53 18 (25%) G2 S Cell Cycle

  15. 56 Aberrations (52% samples)

  16. PI3K/AKT RTK PTEN PI3K PDK1 PIP3 STK11 AKT AMP TSC1/2 Rheb RICTOR RAPTOR mTOR p70S6K 4EBP1

  17. PI3K/AKT RTK PTEN 9 (13%) 2 PI3K PDK1 PIP3 1 STK11 AKT AMP TSC1/2 2 Rheb 1 RICTOR RAPTOR mTOR 1 p70S6K 4EBP1

  18. 16 Aberrations (17% samples)

  19. 19 RTK Amplifications, 3 RTK Activating Mutations

  20. Summary • Exome sequencing identified more alterations v. allele-specific analysis • Alterations in sarcomas are heterogeneous • Therapeutic/prognostic relevance unclear (I.e. EGFR amplification  pathway addiction) • Potential to guide clinical studies

  21. MGH J. Shen Z. Duan G. Nielsen F. Hornicek D. Harmon E. Choy Profile Neal Lindeman DFCI J. Butrynski J. Morgan D. D’Adamo S. George G. Demetri C. Raut A. Wagner BWH J. Hornick Acknowledgements

More Related