1. MOLECULAR SUBTYPES IN LEIOMYOSARCOMA Matt van de Rijn, Stanford University Xiangqian Guo 1, Vickie Young Jo 2, Anne M. Mills 3,Shirley X Zhu 1, Cheng-Han Lee 4, Inigo Espinosa 5, Sushama Varma 1, Erna Forgó 1, Trevor Hastie 6, Kristen Ganjoo 7, Andrew H. Beck 8, Robert B West 1, Christopher Fletcher 2, Matt van de Rijn 1 1 Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA 2 Department of Pathology, Brigham and Women’s Hospital, Boston, MA, 02115, USA 3 Department of Pathology, University of Virginia, Charlottesville, VA, 22904, USA 4 Division of Anatomical Pathology, Royal Alexandra Hospital, Edmonton, Alberta, Canada 5 Department of Pathology, Autonomous University of Barcelona, Barcelona, Spain 6 Department of Statistics, Stanford University, Stanford, CA, 94305, USA 7 Stanford Comprehensive Cancer Center, Stanford University, Stanford, CA, 94305, USA 8 Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, 02115, USA Unbiased search for subtypes

2. - - gene expression profiling of frozen tissues of 51 LMS cases using gene arrays (Oncogene. 2010:29:845-54) - - 3 subtypes, immunohistochemistry markers for one subtype

3. New data: FFPE-compatible next generation sequencing approach “3SEQ” on 99 cases of LMS

4. Similar results in analysis of 82 LMS TCGA dataset

5. Comparison of 3SEQ and TCGA dataset 3SEQ TCGA

6. 70 “core” cases of LMS 70 “core” cases

7. Type 1-LM/myometrium, Type II-UPS

8. IHC markers

9. Subtype assigned by IHC on outcome TMA

11. Targets unique to LMS subtypes

12. Conclusions An unbiased search reveals at least 3 molecular subtypes in LMS Found in 3 independent datasets with 3 distinct methods Subtypes independent from grade, site Subtypes show different clinical behavior Findings suggest different response to range of novel drugs