Examining the Role of Extrachromosomal DNA in 1,216 Lung Cancers

  1. Azhar Khandekar
  2. Phuc H. Hoang
  3. Jens Luebeck
  4. Marcos Díaz-Gay
  5. Wei Zhao
  6. John P. McElderry
  7. Caleb Hartman
  8. Mona Miraftab
  9. Olivia W. Lee
  10. Kara M. Barnao
  11. Erik N. Bergstrom
  12. Yang Yang
  13. Martin A. Nowak
  14. Nathaniel Rothman
  15. Robert Homer
  16. Soo-Ryum Yang
  17. Qing Lan
  18. David C. Wedge
  19. Lixing Yang
  20. Stephen J. Chanock
  21. Tongwu Zhang
  22. Ludmil B. Alexandrov
  23. Maria Teresa Landi
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Abstract

The role of extrachromosomal DNA (ecDNA) in lung cancer, particularly in subjects who never smoked (LCINS), remains unclear. Examination of 1,216 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.

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