MOLECULAR SUBTYPES IN LEIOMYOSARCOMA Matt van de Rijn, Stanford University Xiangqian Guo 1, Vickie...
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Transcript of MOLECULAR SUBTYPES IN LEIOMYOSARCOMA Matt van de Rijn, Stanford University Xiangqian Guo 1, Vickie...
![Page 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.](https://reader034.fdocuments.us/reader034/viewer/2022051621/56649ec65503460f94bd225c/html5/thumbnails/1.jpg)
MOLECULAR SUBTYPES IN LEIOMYOSARCOMA
Matt van de Rijn, Stanford University
Xiangqian Guo1, Vickie Young Jo2, Anne M. Mills3,Shirley X Zhu1, Cheng-Han Lee4, Inigo Espinosa5, Sushama Varma1, Erna Forgó1, Trevor Hastie6,
Kristen Ganjoo7, Andrew H. Beck8, Robert B West1, Christopher Fletcher2, Matt van de Rijn1
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, USA3 Department of Pathology, University of Virginia, Charlottesville, VA, 22904, USA
4 Division of Anatomical Pathology, Royal Alexandra Hospital, Edmonton, Alberta, Canada5 Department of Pathology, Autonomous University of Barcelona, Barcelona, Spain
6 Department of Statistics, Stanford University, Stanford, CA, 94305, USA7 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
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- - 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
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New data: FFPE-compatible next generation sequencing approach “3SEQ” on 99 cases of LMS
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Similar results in analysis of 82 LMS TCGA dataset
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Comparison of 3SEQ and TCGA dataset
3SEQ
TCGA
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70 “core” cases of LMS
70 “core” cases
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Type 1-LM/myometrium, Type II-UPS
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IHC markers
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Subtype assigned by IHC on outcome TMA
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Subtype assigned by IHC on outcome TMA
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Gene Therapeutic Agents Genes over-expressed in subtype I ARAF Sorafenib, Vemurafenib, Dabrafenib, RAF inhibitors CCNE1 CKD2 inhibitor KDR KDR inhibitors NOTCH1 Notch Inhibitors FGFR2 FGFR Inhibitors FGFR1 FGFR Inhibitors Genes over-expressed in subtype II MCL1 Tubulins CDK4 CDK4/6 inhibitors CTNNB1 WNT inhibitors AURKA AURKA Inhibitors RHEB MTOR inhibitors CCND2 CDK4/6 inhibitors CCND1 Hormone therapy, CDK4/6 inhibitors MTOR Everolimus, Temsirolimus, MTOR inhibitors MAPK3 Erlotinib, Gefitinib, EGFR Inhibitors MAPK1 Erlotinib, Gefitinib, EGFR Inhibitors CCND3 CDK4/6 inhibitors NOTCH2 Notch Inhibitors MAP2K2 MEK inhibitors Genes over-expressed in subtype III MDM4 MDM4 inhibitors ERBB3 Pertuzumab EPHA3 Dasatinib, Ephrin inhibitors ESR1 Hormonal therapy Genes over-expressed in subtype II and III EGFR Erlotinib, Gefitinib, EGFR Inhibitors
Targets unique to LMS subtypes
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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