Genomic analysis of early-stage lung cancer reveals a role for TP53 mutations in distant metastasis
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, Jose‐Ezequiel Martín, Oscar M. Rueda, Stephen‐John Sammut, Dilrini De Silva, Ka–Jia Cao, Allison P. Heath, Marilyn M. Li, Jena Lilly, Suzanne P. MacFarland, John M. Maris, Jennifer L. 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
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.