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Distinct Signatures of Lung Cancer Types in Never-Smokers
Lung cancer in never-smokers accounts for 10% to 25% of all lung cancers and is almost always lung adenocarcinoma. Although several studies have catalogued the genomic landscape of lung cancer in smokers, this study is the first to assess a large number of lung cancers in never-smokers.
Researchers from the National Cancer Institute performed whole-genome sequencing on tumors from 232 patients with lung cancer who never smoked. They found three subtypes defined by somatic copy number alterations; these subtypes differ substantially from lung adenocarcinoma in smokers. They termed these subtypes “piano,” “mezzo-forte,” and “forte,” after the musical terms that denote variations in loudness. The “piano” tumors accounted for almost half of the samples and included carcinoid tumors; these tumors had low tumor mutational burdens, long telomeres, and low growth rates. Driver gene mutations in the “piano” group suggest stem cell–like features. About one third of tumors were “mezzo-forte” tumors, almost half of which had specific chromosomal arm-level mutations or EGFR mutations and were associated with a shorter latency period. The most aggressive tumors were in the “forte” group; these tumors were dominated by whole-genome doubling mutations, short telomeres, and aggressive behavior and were most like lung cancer in smokers.
Comment
This study gives us a deeper understanding of lung cancer in never-smokers. The findings could lead to improvements in treatment selection (e.g., avoidance of frontline immunotherapy in some patients and adjuvant chemotherapy in others) and, eventually, prevention and screening in at-risk patients.
Citation(s)
Author:
Zhang T et al.
Title:
Genomic and evolutionary classification of lung cancer in never smokers.
Source:
Nat Genet
2021
Sep
; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
Jyoti D. Patel, MD, FASCO