Genomic analysis of early-stage lung cancer reveals a role for TP53 mutations in distant metastasis
Authors: Van Egeren Debra , Kohli Khushi , Warner Jeremy L. , Bedard Philippe L. , Riely Gregory , Lepisto Eva , Schrag Deborah , LeNoue-Newton Michele , Catalano Paul , Kehl Kenneth L. , Michor Franziska ,   for the AACR Project GENIE Consortium represented by Shawn Sweeney, Fiandalo Michael , Foti Margaret , Khotskaya Yekaterina , Lee Jocelyn , Peters Nicole , Sweeney Shawn , Abraham Jean , Brenton James D. , Caldas Carlos , Doherty Gary , Nimmervoll Birgit , Pinilla Karen , Martin Jose-Ezequiel , Rueda Oscar M. , Sammut Stephen-John , Silva Dilrini , Cao Kajia , Heath Allison P. , Li Marilyn , Lilly Jena , MacFarland Suzanne , Maris John M. , Mason Jennifer L. , Morgan Allison M. , Resnick Adam , Welsh Mark , Zhu Yuankun , Johnson Bruce , Li Yvonne , Sholl Lynette , Beaudoin Ron , Biswas Roshni , Cerami Ethan , Cushing Oya , Dand Deepa , Ducar Matthew , Gusev Alexander , Hahn William C. , Haigis Kevin , Hassett Michael , Janeway Katherine A. , Jänne Pasi , Jawale Arundhati , Johnson Jason , Kehl Kenneth L. , Kumari Priti , Laucks Valerie , Lepisto Eva , Lindeman Neal , Lindsay James , Lueders Amanda , Macconaill Laura , Manam Monica , Mazor Tali , Miller Diana , Newcomb Ashley , Orechia John , Ovalle Andrea , Postle Asha , Quinn Daniel , Reardon Brendan , Rollins Barrett , Shivdasani Priyanka , Tramontano Angela , Van Allen Eliezer , Van Nostrand Stephen C. , Bell Jonathan , Datto Michael B. , Green Michelle , Hubbard Chris , McCall Shannon J. , Mettu Niharika B. , Strickler John H. , Andre Fabrice , Besse Benjamin , Deloger Marc , Dogan Semih , Italiano Antoine , Loriot Yohann , Ludovic Lacroix , Michels Stefan , Scoazec Jean , Tran-Dien Alicia , Vassal Gilles , Freeman Christopher E. , Hsiao Susan J. , Ingham Matthew , Pang Jiuhong , Rabadan Raul , Roman Lira Camille , Carvajal Richard , DuBois Raymond , Arcila Maria E. , Benayed Ryma , Berger Michael F. , Bhuiya Marufur , Brannon A. Rose , Brown Samantha , Chakravarty Debyani , Chu Cynthia , de Bruijn Ino , Galle Jesse , Gao Jianjiong , Gardos Stu , Gross Benjamin , Kundra Ritika , Kung Andrew L. , Ladanyi Marc , Lavery Jessica A. , Li Xiang , Lisman Aaron , Mastrogiacomo Brooke , McCarthy Caroline , Nichols Chelsea , Ochoa Angelica , Panageas Katherine S. , Philip John , Pillai Shirin , Riely Gregory J. , Rizvi Hira , Rudolph Julia , Sawyers Charles L. , Schrag Deborah , Schultz Nikolaus , Schwartz Julian , Sheridan Robert , Solit David , Wang Avery , Wilson Manda , Zehir Ahmet , Zhang Hongxin , Zhao Gaofei , Ahmed Lailah , Bedard Philippe L. , Bruce Jeffrey P. , Chow Helen , Cooke Sophie , Del Rossi Samantha , Felicen Sam , Hakgor Sevan , Jagannathan Prasanna , Kamel-Reid Suzanne , Krishna Geeta , Leighl Natasha , Lu Zhibin , Nguyen Alisha , Oldfield Leslie , Plagianakos Demi , Pugh Trevor J. , Rizvi Alisha , Sabatini Peter , Shah Elizabeth , Singaravelan Nitthusha , Siu Lillian , Srivastava Gunjan , Stickle Natalie , Stockley Tracy , Tang Marian , Virtaenen Carlos , Watt Stuart , Yu Celeste , Bernard Brady , Bifulco Carlo , Cramer Julie L. , Lee Soohee , Piening Brian , Reynolds Sheila , Slagel Joseph , Tittel Paul , Urba Walter , VanCampen Jake , Weerasinghe Roshanthi , Acebedo Alyssa , Guinney Justin , Guo Xindi , Hunter-Zinck Haley , Yu Thomas , Dang Kristen , Anagnostou Valsamo , Baras Alexander , Brahmer Julie , Gocke Christopher , Scharpf Robert B. , Tao Jessica , Velculescu Victor E. , Alexander Shlece , Bailey Neil , Gold Philip , Bierkens Mariska , de Graaf Jan , Hudeček Jan , Meijer Gerrit A. , Monkhorst Kim , Samsom Kris G. , Sanders Joyce , Sonke Gabe , ten Hoeve Jelle , van de Velde Tony , van den Berg José , Voest Emile , Steinhardt George , Kadri Sabah , Pankhuri Wanjari , Wang Peng , Segal Jeremy , Moung Christine , Espinosa-Mendez Carlos , Martell Henry J. , Onodera Courtney , Quintanar Alfaro Ana , Sweet-Cordero E. Alejandro , Talevich Eric , Turski Michelle , Van’t Veer Laura , Wren Amanda , Aguilar Susana , Dienstmann Rodrigo , Mancuso Francesco , Nuciforo Paolo , Tabernero Josep , Viaplana Cristina , Vivancos Ana , Anderson Ingrid , Chaugai Sandip , Coco Joseph , Fabbri Daniel , Johnson Doug , Jones Leigh , Li Xuanyi , Lovly Christine , Mishra Sanjay , Mittendorf Kathleen , Wen Li , Yang Yuanchu James , Ye Chen , Holt Marilyn , LeNoue-Newton Michele L. , Micheel Christine M. , Park Ben H. , Rubinstein Samuel M. , Stricker Thomas , Wang Lucy , Warner Jeremy , Guan Meijian , Jin Guangxu , Liu Liang , Topaloglu Umit , Urtis Cetin , Zhang Wei , D’Eletto Michael , Hutchison Stephen , Longtine Janina , Walther Zenta 
Published: November 2022

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.