Medulloblastomas are the most common malignant brain tumors of childhood, with overall mortality of 40 to 50 percent. Yet their pathogenesis is largely unknown, their cell of origin is debated and their outcome is difficult to predict. My laboratory is addressing these questions, focusing on how genes that regulate cerebellar development become disrupted to promote medulloblastoma growth.
Our lab has measured genome-wide gene expression and chromosome copy-number profiles of medulloblastoma. We have shown that medulloblastomas arise from cerebellar neuronal progenitors, resolving a decades-long dispute on their origin. Examining the molecular profiles further, we have found that as many as six medulloblastoma subtypes can be identified. Each has a unique genetic and molecular "fingerprint" that reflects the mechanisms that drive tumorigenesis and that render the tumor resistant to conventional treatment with chemotherapy and radiation.
Our lab is now investigating these molecular profiles to identify targets for new therapies that can supplement or even replace conventional therapies.
Click here to see the molecular "fingerprints" of different types of medulloblastomas.
We have used supervised learning classification algorithms to identify differences in gene expression between patients who survived after treatment and those who succumbed to their disease. Outcome prediction models, based on these gene expression profiles, are by far the most accurate predictors of medulloblastoma outcome currently available. These models have been incorporated into therapeutic protocols conducted by the national cancer cooperative, the Boston Children's Oncology Group.
About Scott Pomeroy
Scott Pomeroy received his MD and PhD from the University of Cincinnati College of Medicine. He completed an internship at Boston Children's Hospital, a residency at Barnes Hospital (St. Louis, Missouri) and a fellowship in Child Neurology at St. Louis Children's Hospital and Washington University St. Louis. He returned to Boston Children's Hospital in 1991 to join the faculty of the Department of Neurology. Pomeroy was the first recipient of the Compassionate Caregiver Award of the Kenneth Schwartz Center in 1999, and received the Sidney Carter Award from the American Academy of Neurology and the Daniel Drake Medal from the University of Cincinnati for his work on medulloblastoma. He currently is the Neurologist-in-Chief of Boston Children's Hospital and the Director of the Intellectual and Developmental Disabilities Research Center of Boston Children's Hospital and Harvard Medical School.
Scott Pomeroy's Clinical Profile
Scott Pomeroy's IDDRC Homepage
Brain Tumor Program
- Cho YJ, et al. Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J Clin Oncol 2010 Dec 6; [EPub ahead of print].
- Beroukhim R, et al. The landscape of copy number alterations across multiple human cancers. Nature 2010; 463(7283):899-905.
- Subramanian A, et al. Gene Set Enrichment Analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 2005; 102:15545-50.
- Kim JYH, et al. Medulloblastoma tumorigenesis diverges from cerebellar granule cell differentiation in patched heterozygous mice. Dev. Biol 2003; 263:50-66.
- Pomeroy SL, et al. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 2002; 415:436-42.
For a list of Scott Pomeroy's publications on PubMed, click here.