Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients
Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients
Progression to metastatic disease remains the main cause of cancer death. Yet, the underlying genomic mechanisms driving metastasis remain largely unknown. Here, we present MSK-MET, an integrated pan-cancer cohort of tumor genomic and clinical outcome data from more than 25,000 patients. We analyzed this dataset to identify associations between tumor genomic alterations and patterns of metastatic dissemination across 50 tumor types. We found that chromosomal instability is strongly correlated with metastatic burden in some tumor types, including prostate adenocarcinoma, lung adenocarcinoma and HR-positive breast ductal carcinoma, but not in others, such as colorectal adenocarcinoma, pancreatic adenocarcinoma and high-grade serous ovarian cancer. We also identified specific somatic alterations associated with increased metastatic burden and specific routes of metastatic spread. Our data offer a unique resource for the investigation of the biological basis for metastatic spread and highlight the crucial role of chromosomal instability in cancer progression.
Chatila Walid K.、Iyer Gopakumar、Jarnagin William R.、Varghese Anna M.、Weigelt Britta、Janjigian Yelena Y.、Chakravarty Debyani、Gopalan Anuradha、Reis-Filho Jorge S.、Ladanyi Marc、Gonen Mithat、Morris Michael、Motzer Robert J.、Riely Gregory J.、Safonov Anton、Shoushtari Alexander N.、Teo Min Yuen、Yaeger Rona、Smith Shaleigh A.、Kundra Ritika、Ganesh Karuna、Mastrogiacomo Brooke、lacobuzio-Donahue Christine A.、Rudin Charles M.、Abou-Alfa Ghassan K.、Cercek Andrea、Chi Ping、Feldman Darren、Harding James J.、Hakimi Abraham、Jones David R.、Molena Daniela、Morris Luc、Russo Paul、Singer Samuel、Strong Vivian E.、Shah Sohrab P.、Massague Joan、Sanchez-Vega Francisco、Razavi Pedram、DiNatale Renzo G.、Bakhoum Samuel F.、Zehir Ahmet、Reznik Ed、Nandakumar Subhiksha、Schultz Nikolaus、Postow Michael A.、Berger Michael F.、Garcia-Aguilar Julio、Fong Christopher、Nguyen Bastien、Bochner Bernard、Luthra Anisha、Walch Henry、Voss Martin、Bielski Craig M.、Ho Alan L.、Madupuri Ramyasree、Raj Nitya P.、Zamarin Dmitriy、Chandarlapaty Sarat、Abu-Rustum Nadeem、O?ˉReilly Eileen M.、Solit David B.、Ellenson Lora H.、Aghajanian Carol、Boire Adrienne、Rios-Doria Eric、Robson Mark E.、Zauderer Marjorie G.、Gao Jianjiong、Tap William、Abida Wassim、Rosenberg Jonathan E.
Marie-Jos¨|e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center||Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Surgery, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology, Memorial Sloan Kettering Cancer CenterDepartment of Pathology, Memorial Sloan Kettering Cancer CenterDepartment of Pathology, Memorial Sloan Kettering Cancer CenterDepartment of Pathology, Memorial Sloan Kettering Cancer CenterDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterMarie-Jos¨|e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center||Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterMarie-Jos¨|e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center||Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterMolecular Pharmacology Program, Sloan Kettering Institute||Department of Medicine, Memorial Sloan Kettering Cancer CenterMarie-Jos¨|e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center||Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Pathology, Memorial Sloan Kettering Cancer CenterMolecular Pharmacology Program, Sloan Kettering Institute||Department of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterWeill Medical College at Cornell University||Department of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Surgery, Memorial Sloan Kettering Cancer CenterDepartment of Surgery, Memorial Sloan Kettering Cancer CenterDepartment of Surgery, Memorial Sloan Kettering Cancer CenterDepartment of Surgery, Memorial Sloan Kettering Cancer CenterDepartment of Surgery, Memorial Sloan Kettering Cancer CenterDepartment of Surgery, Memorial Sloan Kettering Cancer CenterDepartment of Surgery, Memorial Sloan Kettering Cancer CenterDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterCancer Biology and Genetics Program, Sloan Kettering InstituteDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center||Department of Surgery, Memorial Sloan Kettering Cancer CenterWeill Medical College at Cornell University||Department of Medicine, Memorial Sloan Kettering Cancer CenterMolecular Pharmacology Program, Sloan Kettering Institute||Urology and Renal Transplantation Service, Virginia Mason Medical CenterHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer CenterDepartment of Pathology, Memorial Sloan Kettering Cancer CenterMarie-Jos¨|e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center||Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterMarie-Jos¨|e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center||Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterMarie-Jos¨|e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center||Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterMarie-Jos¨|e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center||Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Pathology, Memorial Sloan Kettering Cancer CenterDepartment of Surgery, Memorial Sloan Kettering Cancer CenterMarie-Jos¨|e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center||Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterMarie-Jos¨|e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center||Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterDepartment of Surgery, Memorial Sloan Kettering Cancer CenterMarie-Jos¨|e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center||Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterMarie-Jos¨|e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center||Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Weill Medical College at Cornell UniversityDepartment of Medicine, Memorial Sloan Kettering Cancer CenterMarie-Jos¨|e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center||Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterWeill Medical College at Cornell University||Department of Medicine, Memorial Sloan Kettering Cancer CenterHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Surgery, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterMarie-Jos¨|e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center||Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Weill Medical College at Cornell University||Department of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer CenterDepartment of Surgery, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterMarie-Jos¨|e and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center||Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center||Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Memorial Sloan Kettering Cancer Center
肿瘤学医学研究方法基础医学
Chatila Walid K.,Iyer Gopakumar,Jarnagin William R.,Varghese Anna M.,Weigelt Britta,Janjigian Yelena Y.,Chakravarty Debyani,Gopalan Anuradha,Reis-Filho Jorge S.,Ladanyi Marc,Gonen Mithat,Morris Michael,Motzer Robert J.,Riely Gregory J.,Safonov Anton,Shoushtari Alexander N.,Teo Min Yuen,Yaeger Rona,Smith Shaleigh A.,Kundra Ritika,Ganesh Karuna,Mastrogiacomo Brooke,lacobuzio-Donahue Christine A.,Rudin Charles M.,Abou-Alfa Ghassan K.,Cercek Andrea,Chi Ping,Feldman Darren,Harding James J.,Hakimi Abraham,Jones David R.,Molena Daniela,Morris Luc,Russo Paul,Singer Samuel,Strong Vivian E.,Shah Sohrab P.,Massague Joan,Sanchez-Vega Francisco,Razavi Pedram,DiNatale Renzo G.,Bakhoum Samuel F.,Zehir Ahmet,Reznik Ed,Nandakumar Subhiksha,Schultz Nikolaus,Postow Michael A.,Berger Michael F.,Garcia-Aguilar Julio,Fong Christopher,Nguyen Bastien,Bochner Bernard,Luthra Anisha,Walch Henry,Voss Martin,Bielski Craig M.,Ho Alan L.,Madupuri Ramyasree,Raj Nitya P.,Zamarin Dmitriy,Chandarlapaty Sarat,Abu-Rustum Nadeem,O?ˉReilly Eileen M.,Solit David B.,Ellenson Lora H.,Aghajanian Carol,Boire Adrienne,Rios-Doria Eric,Robson Mark E.,Zauderer Marjorie G.,Gao Jianjiong,Tap William,Abida Wassim,Rosenberg Jonathan E..Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients[EB/OL].(2025-03-28)[2025-05-12].https://www.biorxiv.org/content/10.1101/2021.06.28.450217.点此复制
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