Examining the role of extrachromosomal DNA in lung cancer.

Khandekar, Azhar; Hoang, Phuc H; Luebeck, Jens; Díaz-Gay, Marcos; Zhao, Wei; McElderry, John P; Hartman, Caleb; Miraftab, Mona et al. · J Natl Cancer Inst · 2026

basic_science · Level V

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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 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.