Sherlock-Lung: Tracing Lung Cancer Mutational Processes in Never Smokers

art showing a human lung with magnifying glass, which reveals DNA

Results from Sherlock-lung Published in Nature Genetics

This study describes for the first time three molecular subtypes of lung cancer in people who have never smoked.

Sherlock-Lung is a comprehensive study that aims to trace lung cancer etiology in never smokers by analyzing genomic data in tumor and surrounding lung tissue. Whole genome sequencing, whole transcriptome, genome-wide methylation, and microbiome data are being analyzed to characterize the genomic landscape of lung cancer in never smokers (LCINS) and to identify exogenous and endogenous processes involved in lung tumorigenesis. Analysis of the tumor cells of origin, normal-to-tumor evolution, and tumor microenvironment will be conducted in a subgroup of the cases also using single/oligo cell sequencing approaches. The molecular landscape will be integrated with histological and radiological features to develop a more refined classification of LCINS and provide insights into prognosis and treatment strategies.

The study will include 2,000 never-smoking lung cancer patients, a subset (n=~300) with “special exposures,” such as indoor and outdoor air pollution, radon, asbestos, previous lung diseases, etc. The remaining ~1700 cases will come from the “general population,” with unknown exposures to lung cancer risk factors.

For more information, please contact Maria Teresa Landi, M.D., Ph.D.

Tracing Lung Cancer Risk Factors Through Mutational Signatures in Never Smokers: the Sherlock-Lung Study. American Journal of Epidemiology 2021; Landi MT, Synnott NC, et al.