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Genomic analysis of early-stage lung cancer reveals a role for TP53 mutations in distant metastasis

2022; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês

10.1038/s41598-022-21448-1

2045-2322

Debra Van Egeren, Khushi Kohli, Jeremy L. Warner, Philippe L. Bédard, Gregory J. Riely, Eva M. Lepisto, Deborah Schrag, Michele L. Lenoue-Newton, Paul J. Catalano, Kenneth L. Kehl, Franziska Michor, Michael V. Fiandalo, Margaret Foti, Yekaterina B. Khotskaya, Jocelyn Lee, Nicole Peters, Shawn M. Sweeney, Jean Abraham, James D. Brenton, Carlos Caldas, Gary J. Doherty, Birgit Nimmervoll, Karen Pinilla, José-Ezequiel Martín, Oscar M. Rueda, Stephen‐John Sammut, Dilrini Silva, Ka–Jia Cao, Allison P. Heath, Marilyn M. Li, Jena Lilly, Suzanne P. MacFarland, John M. Maris, Jennifer Mason, Allison M. Morgan, Adam Resnick, Mark Welsh, Yuankun Zhu, Bruce E. Johnson, Yvonne Li, Lynette M. Sholl, Ron Beaudoin, Roshni Biswas, Ethan Cerami, Oya Cushing, Deepa Dand, Matthew D. Ducar, Alexander Gusev, William C. Hahn, Kevin M. Haigis, Michael J. Hassett, Katherine A. Janeway, Pasi A. Jänne, Arundhati Jawale, Jason M. Johnson, Kenneth L. Kehl, Priti Kumari, Valerie Laucks, Eva M. Lepisto, Neal I. Lindeman, James Lindsay, Amanda Lueders, Laura E. MacConaill, Monica Manam, Tali Mazor, Diana Miller, Ashley Newcomb, John A. Orechia, Andrea Ovalle, Asha Postle, Daniel M. Quinn, Brendan Reardon, Barrett J. Rollins, Priyanka Shivdasani, Angela C. Tramontano, Eliezer M. Van Allen, Stephen C. Van Nostrand, Jonathan L. Bell, Michael Datto, Michelle Green, Chris Hubbard, Shannon J. McCall, Niharika B. Mettu, John H. Strickler, Fabrice André, Benjamin Besse, Marc Deloger, Semih Doğan, Antoîne Italiano, Yohann Loriot, Lacroix Ludovic, Stefan Michels, Jean Scoazec, Alicia Tran-Dien, Gilles Vassal, Christopher E. Freeman, Susan J. Hsiao, Matthew Ingham, Jiuhong Pang, Raúl Rabadán, Lira Camille Roman, Richard D. Carvajal, Raymond N. DuBois, Maria E. Arcila, Ryma Benayed, Michael F. Berger, Marufur Bhuiya, A. Rose Brannon, Samantha Brown, Debyani Chakravarty, Cynthia Chu, Ino de Bruijn, Jesse Galle, Jianjiong Gao, Stuart M. Gardos, Benjamin Groß, Ritika Kundra, Andrew L. Kung, Marc Ladanyi, Jessica A. Lavery, Xiang Li, Aaron Lisman, Brooke Mastrogiacomo, Caroline G. McCarthy, Chelsea Nichols, Angelica Ochoa, Katherine S. Panageas, John Philip, Shirin Pillai, Gregory J. Riely, Hira Rizvi, Julia E. Rudolph, Charles L. Sawyers, Deborah Schrag, Nikolaus Schultz, J. Schwartz, Robert P. Sheridan, David B. Solit, Avery Wang, Manda Wilson, Ahmet Zehir, Hongxin Zhang, Gaofei Zhao, Lailah Ahmed, Philippe L. Bédard, Jeffrey P. Bruce, Helen Chow, Sophie Cooke, Samantha Del Rossi, Sam Felicen, Sevan Hakgor, Prasanna Jagannathan, Suzanne Kamel‐Reid, Geeta Krishna, Natasha B. Leighl, Zhibin Lu, Alisha Nguyen, Leslie E. Oldfield, Demi Plagianakos, Trevor J. Pugh, Alisha Rizvi, Peter Sabatini, Elizabeth Shah, Nitthusha Singaravelan, Lillian L. Siu, Gunjan Srivastava, Natalie Stickle, Tracy Stockley, Marian Tang, Carlos Virtaenen, Stuart Watt, Celeste Yu, Brady Bernard, Carlo Bifulco, Julie Cramer, Soohee Lee, Brian Piening, Sheila M. Reynolds, Joseph Slagel, Paul Tittel, Walter J. Urba, Jake VanCampen, Roshanthi Weerasinghe, Alyssa Acebedo, Justin Guinney, Xindi Guo, Haley Hunter-Zinck, Thomas Yu, Kristen K. Dang, Valsamo Anagnostou, Alexander S. Baras, Julie R. Brahmer, Christopher D. Gocke, Robert B. Scharpf, Jessica J. Tao, Victor E. Velculescu, Shlece Alexander, Neil A. Bailey, Philip W. Gold, Mariska Bierkens, J. de Graaf, Jan Hudeček, Gerrit A. Meijer, Kim Monkhorst, Kris G. Samsom, Joyce Sanders, Gabe S. Sonke, Jelle ten Hoeve, Tony van de Velde, José van den Berg, Emile E. Voest, George F. Steinhardt, Sabah Kadri, Wanjari Pankhuri, Peng Wang, Jeremy P. Segal, Christine Moung, Carlos Espinosa-Mendez, Henry J. Martell, Courtney Onodera, Ana Quintanar Alfaro, E. Alejandro Sweet‐Cordero, Eric Talevich, Michelle L. Turski, Laura van’t Veer, Amanda Wren, Susana Aguilar, Rodrigo Dienstmann, Francesco M. Mancuso, Paolo Nucíforo, Josep Tabernero, Cristina Viaplana, Ana Vivancos, Ingrid Anderson, Sandip Chaugai, Joseph Coco, Daniel Fabbri, Doug Johnson, Leigh F. Jones, Xuanyi Li, Christine M. Lovly, Sanjay Mishra, Kathleen F. Mittendorf, Wen Li, Yuanchu James Yang, Chen Ye, Marilyn Holt, Michele L. Lenoue-Newton, Christine Micheel, Ben Ho Park, Samuel M. Rubinstein, Thomas Stricker, Lucy Lu Wang, Jeremy L. Warner, Meijian Guan, Guangxu Jin, Liang Liu, Ümit Topaloğlu, Cetin Urtis, Wei Zhang, Michael D’Eletto, Stephen Hutchison, Janina A. Longtine, Zenta Walther,

RNA modifications and cancer

Abstract Patients with non-small cell lung cancer (NSCLC) who have distant metastases have a poor prognosis. To determine which genomic factors of the primary tumor are associated with metastasis, we analyzed data from 759 patients originally diagnosed with stage I–III NSCLC as part of the AACR Project GENIE Biopharma Collaborative consortium. We found that TP53 mutations were significantly associated with the development of new distant metastases. TP53 mutations were also more prevalent in patients with a history of smoking, suggesting that these patients may be at increased risk for distant metastasis. Our results suggest that additional investigation of the optimal management of patients with early-stage NSCLC harboring TP53 mutations at diagnosis is warranted in light of their higher likelihood of developing new distant metastases.