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Does a History of Smoking Influence the Molecular Diversity of Lung Tumors?

By: Justine Landin, PhD
Posted: Tuesday, December 1, 2020

The reportedly largest comprehensive study of lung cancer proteogenomics was recently conducted in an East-Asian population. Compared with smokers, nonsmokers appeared to have a diverse molecular tumor profile, which may have accounted for a difference in response to targeted therapies. In addition, nonsmokers with lung cancer exhibited select genetic fault patterns that were dependent upon age and sex. Work from this multicenter study was published in the journal Cell by principal investigator Yu-Ju Chen, MD, of Academia Sinica, Taiwan, and colleagues. The researchers were optimistic that these findings may extend to other populations.

“This new study...reveals new ways of telling apart patients with different tumor characteristics that could be exploited with tailored treatment strategies,”stated Paul Workman, PhD, Chief Executive of The Institute of Cancer Research, London, in a press release.

The prospective study included 103 treatment-naive female (58%) and male (42%) patients with lung cancer from Taiwan. Of note, unlike other lung cancer genomics studies, the majority of these patients were nonsmokers (83%). Histologic examination revealed that 89% of tumors were adenocarcinomas, and 80% were early stage IA or IB tumors. Extensive probing of tumor properties included somatic mutations, environmental mutational signatures, proteomic subtypes, phosphorylation alterations, and protein co-variation networks.

The highest prevalence of APOBEC mutational signatures was observed in younger women, and this was associated with higher progression-free survival, particularly if these patients had EGFR wild-type tumors. Older women, compared with men and younger women, were more likely to exhibit environmental carcinogen-like mutational signatures, such as nitrosamine and nitro polycyclic aromatic hydrocarbons (PAHs). Of note, nitrosamine and nitro PAHs signatures were prominent in nonsmokers alone and were found to be positively correlated with the APOBEC signature.

This study provides an in-depth examination of multiple tumor characteristics that may inform future diagnosis and treatment of nonsmokers with lung cancer.

Disclosure: For full disclosures of the study authors, see cell.com.



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