DOI: 10.1093/jnci/djag273 ISSN: 0027-8874
Examining the role of extrachromosomal DNA in lung cancer
Azhar Khandekar, Phuc H Hoang, Jens Luebeck, Marcos Díaz-Gay, Wei Zhao, John P McElderry, Caleb Hartman, Mona Miraftab, Olivia W Lee, Kara M Barnao, Kristine Jones, Amy Hutchinson, Belynda Hicks, Erik N Bergstrom, Yang Yang, Martin A Nowak, Nathaniel Rothman, Angela C Pesatori, Dario Consonni, Robert Homer, Marina K Baine, Lynette M Sholl, Philippe Joubert, Charles Leduc, William D Travis, Soo-Ryum Yang, Qing Lan, David C Wedge, Lixing Yang, Stephen J Chanock, Tongwu Zhang, Ludmil B Alexandrov, Maria Teresa LandiAbstract
The role of extrachromosomal DNA (ecDNA) in lung cancer, particularly in subjects who never smoked (LCINS), remains unclear. Examination of over 1200 whole-genome-sequenced lung cancers identified ecDNA in 18.9% of patients. Recurrent amplification of MDM2 and other oncogenes via ecDNA possibly drives a LCINS subset. Tumors harboring ecDNA showed worse overall survival than tumors harboring other focal amplifications. A strong association with whole-genome doubling suggests most ecDNA reflects genomic instability in treatment-naïve lung cancer.