Talk by Scott Tomlins

TALK BY  Scott A. Tomlins, MD, PhD
Assistant Professor of Pathology and Urology
University of Michigan Medical School
Ann Arbor, MI USA

Title: Molecular Subtyping of Prostate Cancer:
Translating Biology to the Clinic

Wednesday, April 17 2013, 11 AM, in CPR Greenhouse seminar room (6.2.09), Panum

All are welcome

Molecular Subtyping of Prostate Cancer: Translating Biology to the Clinic
Scott A. Tomlins, M.D., Ph.D.
Assistant Professor, Departments of Pathology and Urology
University of Michigan Medical School,
Ann Arbor, MI  USA 

Profiling and integrative analysis of the prostate cancer transcriptome, genome and metabolome has identified chromosomal rearrangements, copy number gains/losses, mutations, genes with outlier expression and transcriptional programs that drive prostate cancer development and progression. For example, genome wide characterization of prostate cancer has led to the identification of recurrent gene fusions involving ETS transcription factors (most commonly TMPRSS2:ERG) in approximately half of all prostate cancers. Similarly, mutations in SPOP have been identified in 5~10% of prostate cancers, which are exclusively ETS fusion negative. Lessons learned from leveraging large, disparate data sources to understand disease biology will be discussed. Results from comprehensive characterization of the prostate cancer genome and a novel clinical trial based on comprehensive genomic/transcriptomic assessment of tumors from patients with late stage cancer in real time (MI-ONCOSEQ) will be highlighted. 

Additionally, although advancements in molecular pathology have transformed the routine pathological evaluation of several common carcinomas (such as breast and lung), evaluation of prostate cancer is still based almost entirely on morphology. Here, I will discuss the challenges of translating the molecular knowledge of prostate cancer described above into biomarkers that can impact clinical practice, focusing on the challenges of assessing protein products. Reproducible subtyping of prostate cancer based on ETS gene fusion status in combination with other markers such as SPINK1 and PTEN, is now possible, and the role of subtyping in prostate cancer diagnosis, risk stratification of isolated high grade prostatic intraepithelial neoplasia, and potential applications in prognosis and therapeutic targeting will be addressed. Lastly, areas of research and clinical need that will most impact patient management will be discussed.