New Epigenetic Biomarkers of Oropharyngeal Cancer<br />Thomas J. Belbin<br />Department of Pathology<br />5/21/2010<br />S...
5/21/2010<br />Science at the heart of medicine<br />Head and Neck Squamous Cell Carcinoma<br />>48K cases, >11K deaths in...
Einstein/Montefiore Head and Neck Cancer Research Group<br />5/21/2010<br />Science at the heart of medicine<br />Programm...
DNA methylation in cancer<br />5/21/2010<br />Science at the heart of medicine<br />
HumanMethylation27 Content Summary<br />5/21/2010<br />Science at the heart of medicine<br />
Differential DNA methylation in OPSCC<br />5/21/2010<br />Science at the heart of medicine<br />r2=0.96<br />CpG loci with...
Differential DNA methylation in OPSCC<br />5/21/2010<br />Science at the heart of medicine<br />
Distribution of differentially methylated CpG loci on chromosomes 18. Data points are plotted as the average difference in...
5/21/2010<br />Science at the heart of medicine<br />Distribution of differentially methylated CpG loci on chromosomes 19....
5/21/2010<br />Science at the heart of medicine<br />Distribution of differentially methylated CpG loci on chromosomes 19....
Can ZNF671 be pharmacologically re-expressed in a model system?<br />5/21/2010<br />Science at the heart of medicine<br />...
Executive Report<br />5/21/2010<br />Clinically relevant biomarkers<br />
A Computational Approach for HNSCC Biomarker Discovery<br />5/21/2010<br />Science at the heart of medicine<br />N0<br />N...
Signatures of DNA methylation are predictive of outcome in oropharyngeal squamous cell carcinoma<br />5/21/2010<br />Scien...
a distant metastasis
treatment for persistent disease
Upcoming SlideShare
Loading in …5
×

Session 1.5: Belbin

504 views

Published on

Tom Belbin

Published in: Health & Medicine
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
504
On SlideShare
0
From Embeds
0
Number of Embeds
6
Actions
Shares
0
Downloads
0
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Session 1.5: Belbin

  1. 1. New Epigenetic Biomarkers of Oropharyngeal Cancer<br />Thomas J. Belbin<br />Department of Pathology<br />5/21/2010<br />Science at the heart of medicine<br />
  2. 2. 5/21/2010<br />Science at the heart of medicine<br />Head and Neck Squamous Cell Carcinoma<br />>48K cases, >11K deaths in the US<br />oral cavity, oropharynx, hypopharynx, larynx, nasopharynx<br />tobacco, alcohol, HPV, betel quid etc.<br />surgery, radiation, chemotherapy<br />recurrence in about 50% of patients<br />5-year survival rate (~50%)<br />no molecular markers<br />
  3. 3. Einstein/Montefiore Head and Neck Cancer Research Group<br />5/21/2010<br />Science at the heart of medicine<br />Programmatic Goals:<br />Predict tumor behavior<br />Optimize treatment selection<br />Identify potential new therapeutic targets<br />Einstein Head and Neck Cancer Research Group: Belbin et al. (2007). Head and neck cancer: reduce and integrate for optimal outcome. Cytogenet Genome Res 118:92–109.<br />
  4. 4. DNA methylation in cancer<br />5/21/2010<br />Science at the heart of medicine<br />
  5. 5. HumanMethylation27 Content Summary<br />5/21/2010<br />Science at the heart of medicine<br />
  6. 6. Differential DNA methylation in OPSCC<br />5/21/2010<br />Science at the heart of medicine<br />r2=0.96<br />CpG loci within classically defined CpG island (20,007 loci)<br />CpG loci outside of classically defined CpG island (7,572 loci)<br />
  7. 7. Differential DNA methylation in OPSCC<br />5/21/2010<br />Science at the heart of medicine<br />
  8. 8. Distribution of differentially methylated CpG loci on chromosomes 18. Data points are plotted as the average difference in beta between OPSCC tumor and normal mucosa for the 24 patients in Patient Set 1. Points above the ideogram are identified as hypermethylated in OPSCC; those below the ideogram are identified as hypomethylated.<br />5/21/2010<br />Science at the heart of medicine<br />
  9. 9. 5/21/2010<br />Science at the heart of medicine<br />Distribution of differentially methylated CpG loci on chromosomes 19. Data points are plotted as the average difference in beta between OPSCC tumor and normal mucosa for the 24 patients in Patient Set 1. Points above the ideogram are identified as hypermethylated in OPSCC; those below the ideogram are identified as hypomethylated.<br />
  10. 10. 5/21/2010<br />Science at the heart of medicine<br />Distribution of differentially methylated CpG loci on chromosomes 19. Data points are plotted as the average difference in beta between OPSCC tumor and normal mucosa for the 24 patients in Patient Set 1. Points above the ideogram are identified as hypermethylated in OPSCC; those below the ideogram are identified as hypomethylated.<br />
  11. 11. Can ZNF671 be pharmacologically re-expressed in a model system?<br />5/21/2010<br />Science at the heart of medicine<br />FaDu<br />manipulate expression and study phenotype<br />study mechanism in a model system<br />Belbin et al. (2010). Aberrant DNA Methylation of ZNF Family Nucleic Acid Binding Protein Genes on Chromosome 19 in Oropharyngeal Squamous Cell Carcinoma. Submitted to American Journal of Pathology .<br />
  12. 12. Executive Report<br />5/21/2010<br />Clinically relevant biomarkers<br />
  13. 13. A Computational Approach for HNSCC Biomarker Discovery<br />5/21/2010<br />Science at the heart of medicine<br />N0<br />N+<br />N+<br />N0<br />Support Vector Machine (SVM): machine learning algorithm used to divide samples into predefined groups based on a set of attributes<br />
  14. 14. Signatures of DNA methylation are predictive of outcome in oropharyngeal squamous cell carcinoma<br />5/21/2010<br />Science at the heart of medicine<br />Confusion matrices showing the performance of independent, feature selected SVM models trained to predict for aggressive disease status or nodal metastasis.<br />150 CpG signature<br />Aggressive Disease @ 24 months:<br /><ul><li>a recurring (local, regional) primary tumor
  15. 15. a distant metastasis
  16. 16. treatment for persistent disease
  17. 17. died of disease
  18. 18. 12 out of 36 OP patients</li></ul>Nodal metastasis at diagnosis (N+ vs N0)<br />38 out of 51 OP patients<br />125 CpG signature<br />Lleras et al. (2010). Signatures of DNA methylation are predictive of outcome in head and neck squamous cell carcinoma. Manuscript in preparation.<br />
  19. 19. Future Directions<br />Validate our predictive signatures in external patient populations to develop a clinically useful test for treatment selection at initial diagnosis.<br />Test the functional significance of clinically relevant genes using the cell line model system.<br />What about other anatomic sites?<br />Can other –omics platforms be used to build prognostic signatures? (ex. gene expression, microRNA)<br />5/21/2010<br />Science at the heart of medicine<br />
  20. 20. Acknowledgements<br />5/21/2010<br />Science at the heart of medicine<br />Albert Einstein College of Medicine <br />(www.einstein.yu.edu)<br />Dr. Michael Prystowsky <br />Dr. Geoffrey Childs<br />Dr. Nicolas Schlecht<br />Dr. Thomas Harris<br />Aldo Massimi<br />Nicole Kawachi<br />Leslie Adrien<br />Roberto Lleras<br />Xin Zheng<br />Quan Chen<br />Montefiore Medical Center <br />(www.montefiore.org)<br />Dr. Richard Smith<br />Dr. Brad Schiff<br />Dr. Margie Brandwein-Gensler<br />Dr. Chris Keller<br />Dr. Missak Haigentz<br />Dr. Madhur Garg<br />Cathy Sarta<br />Supported by :<br />NIH Grant # R21CA104402 (TJB)<br />NIH Grant # R21CA131648 (TJB)<br />NIH Grant # R33CA103547 (MBP)<br />Thyroid Head and Neck Cancer (THANC) Foundation (TJB)<br />

×