Integrated genomic profiling expands clinical options for patients with cancer

被引:128
作者
Beaubier, Nike [1 ]
Bontrager, Martin [1 ]
Huether, Robert [1 ]
Igartua, Catherine [1 ]
Lau, Denise [1 ]
Tell, Robert [1 ]
Bobe, Alexandria M. [1 ]
Bush, Stephen [1 ]
Chang, Alan L. [1 ]
Hoskinson, Derick C. [1 ]
Khan, Aly A. [1 ]
Kudalkar, Emily [1 ]
Leibowitz, Benjamin D. [1 ]
Lozachmeur, Ariane [1 ]
Michuda, Jackson [1 ]
Parsons, Jerod [1 ]
Perera, Jason F. [1 ]
Salahudeen, Ameen [1 ]
Shah, Kaanan P. [1 ]
Taxter, Timothy [1 ]
Zhu, Wei [1 ]
White, Kevin P. [1 ]
机构
[1] Tempus Labs Inc, Chicago, IL 60654 USA
关键词
JOINT-CONSENSUS-RECOMMENDATION; MUTATIONAL PROCESSES; SEQUENCE VARIANTS; GASTRIC-CANCER; GENE FUSION; TUMORS; REPAIR; HER3; OVEREXPRESSION; ASSOCIATION;
D O I
10.1038/s41587-019-0259-z
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Genomic analysis of paired tumor-normal samples and clinical data can be used to match patients to cancer therapies or clinical trials. We analyzed 500 patient samples across diverse tumor types using the Tempus xT platform by DNA-seq, RNA-seq and immunological biomarkers. The use of a tumor and germline dataset led to substantial improvements in mutation identification and a reduction in false-positive rates. RNA-seq enhanced gene fusion detection and cancer type classifications. With DNA-seq alone, 29.6% of patients matched to precision therapies supported by high levels of evidence or by well-powered studies. This proportion increased to 43.4% with the addition of RNA-seq and immunotherapy biomarker results. Combining these data with clinical criteria, 76.8% of patients were matched to at least one relevant clinical trial on the basis of biomarkers measured by the xT assay. These results indicate that extensive molecular profiling combined with clinical data identifies personalized therapies and clinical trials for a large proportion of patients with cancer and that paired tumor-normal plus transcriptome sequencing outperforms tumor-only DNA panel testing.
引用
收藏
页码:1351 / +
页数:13
相关论文
共 64 条
[1]   Signatures of mutational processes in human cancer [J].
Alexandrov, Ludmil B. ;
Nik-Zainal, Serena ;
Wedge, David C. ;
Aparicio, Samuel A. J. R. ;
Behjati, Sam ;
Biankin, Andrew V. ;
Bignell, Graham R. ;
Bolli, Niccolo ;
Borg, Ake ;
Borresen-Dale, Anne-Lise ;
Boyault, Sandrine ;
Burkhardt, Birgit ;
Butler, Adam P. ;
Caldas, Carlos ;
Davies, Helen R. ;
Desmedt, Christine ;
Eils, Roland ;
Eyfjord, Jorunn Erla ;
Foekens, John A. ;
Greaves, Mel ;
Hosoda, Fumie ;
Hutter, Barbara ;
Ilicic, Tomislav ;
Imbeaud, Sandrine ;
Imielinsk, Marcin ;
Jaeger, Natalie ;
Jones, David T. W. ;
Jones, David ;
Knappskog, Stian ;
Kool, Marcel ;
Lakhani, Sunil R. ;
Lopez-Otin, Carlos ;
Martin, Sancha ;
Munshi, Nikhil C. ;
Nakamura, Hiromi ;
Northcott, Paul A. ;
Pajic, Marina ;
Papaemmanuil, Elli ;
Paradiso, Angelo ;
Pearson, John V. ;
Puente, Xose S. ;
Raine, Keiran ;
Ramakrishna, Manasa ;
Richardson, Andrea L. ;
Richter, Julia ;
Rosenstiel, Philip ;
Schlesner, Matthias ;
Schumacher, Ton N. ;
Span, Paul N. ;
Teague, Jon W. .
NATURE, 2013, 500 (7463) :415-+
[2]  
Allen J., 2018, J ONCOL NAVIG SURVIV, V9
[3]   AACR Project GENIE: Powering Precision Medicine through an International Consortium [J].
Andre, Fabrice ;
Arnedos, Monica ;
Baras, Alexander S. ;
Baselga, Jose ;
Bedard, Philippe L. ;
Berger, Michael F. ;
Bierkens, Mariska ;
Calvo, Fabien ;
Cerami, Ethan ;
Chakravarty, Debyani ;
Dang, Kristen K. ;
Davidson, Nancy E. ;
Del Vecchio, Fitz Catherine ;
Dogan, Semih ;
DuBois, Raymond N. ;
Ducar, Matthew D. ;
Futreal, P. Andrew ;
Gao Jianjiong ;
Garcia, Francisco ;
Gardos, Stu ;
Gocke, Christopher D. ;
Gross, Benjamin E. ;
Guinney, Justin ;
Heins, Zachary J. ;
Hintzen, Stephanie ;
Horlings, Hugo ;
Hudecek, Jan ;
Hyman, David M. ;
Kamel-Reid, Suzanne ;
Kandoth, Cyriac ;
Kinyua, Walter ;
Kumari, Priti ;
Kundra, Ritika ;
Ladanyi, Marc ;
Lefebvre, Celine ;
LeNoue-Newton, Michele L. ;
Lepisto, Eva M. ;
Levy, Mia A. ;
Lindeman, Neal, I ;
Lindsay, James ;
Liu, David ;
Lu Zhibin ;
MacConaill, Laura E. ;
Ian, Maurer ;
Maxwell, David S. ;
Meijer, Gerrit A. ;
Meric-Bernstam, Funda ;
Micheel, Christine M. ;
Miller, Clinton ;
Mills, Gordon .
CANCER DISCOVERY, 2017, 7 (08) :818-831
[4]  
[Anonymous], 2018, THE ASCO POST
[5]   IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade [J].
Ayers, Mark ;
Lunceford, Jared ;
Nebozhyn, Michael ;
Murphy, Erin ;
Loboda, Andrey ;
Kaufman, David R. ;
Albright, Andrew ;
Cheng, Jonathan D. ;
Kang, S. Peter ;
Shankaran, Veena ;
Piha-Paul, Sarina A. ;
Yearley, Jennifer ;
Seiwert, Tanguy Y. ;
Ribas, Antoni ;
McClanahan, Terrill K. .
JOURNAL OF CLINICAL INVESTIGATION, 2017, 127 (08) :2930-2940
[6]  
Beaubier Nike, 2019, Oncotarget, V10, P2384, DOI 10.18632/oncotarget.26797
[7]   Association of Tumor Mutational Burden With DNA Repair Mutations and Response to Anti-PD-1/PD-L1 Therapy in Non-Small-Cell Lung Cancer [J].
Chae, Young Kwang ;
Davis, Andrew A. ;
Raparia, Kirtee ;
Agte, Sarita ;
Pan, Alan ;
Mohindra, Nisha ;
Villaflor, Victoria ;
Giles, Francis .
CLINICAL LUNG CANCER, 2019, 20 (02) :88-+
[8]   The TMPRSS2-ERG Gene Fusion Blocks XRCC4-Mediated Nonhomologous End-Joining Repair and Radiosensitizes Prostate Cancer Cells to PARP Inhibition [J].
Chatterjee, Payel ;
Choudhary, Gaurav S. ;
Alswillah, Turkeyah ;
Xiong, Xiahui ;
Heston, Warren D. ;
Magi-Galluzzi, Cristina ;
Zhang, Junran ;
Klein, Eric A. ;
Almasan, Alexandru .
MOLECULAR CANCER THERAPEUTICS, 2015, 14 (08) :1896-1906
[9]   UpSetR: an R package for the visualization of intersecting sets and their properties [J].
Conway, Jake R. ;
Lex, Alexander ;
Gehlenborg, Nils .
BIOINFORMATICS, 2017, 33 (18) :2938-2940
[10]   Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy [J].
Cristescu, Razvan ;
Mogg, Robin ;
Ayers, Mark ;
Albright, Andrew ;
Murphy, Erin ;
Yearley, Jennifer ;
Sher, Xinwei ;
Liu, Xiao Qiao ;
Lu, Hongchao ;
Nebozhyn, Michael ;
Zhang, Chunsheng ;
Lunceford, Jared ;
Joe, Andrew ;
Cheng, Jonathan ;
Webber, Andrea L. ;
Ibrahim, Nageatte ;
Plimack, Elizabeth R. ;
Ott, Patrick A. ;
Seiwert, Tanguy ;
Ribas, Antoni ;
McClanahan, Terrill K. ;
Tomassini, Joanne E. ;
Loboda, Andrey ;
Kaufman, David .
SCIENCE, 2018, 362 (6411) :197-+