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WCLC 2020: Genomic Analysis of Women With Lung Cancer Who Never Smoked

By: Vanessa A. Carter, BS
Posted: Wednesday, February 10, 2021

According to Sitapriya Moorthi, PhD, of Fred Hutchinson Cancer Research Center, Seattle, and colleagues, approximately 17% of male and 24% of female lung cancer cases are nonsmokers. These researchers identified enrichment of oncogenes and genetic mutations in never-smoking individuals by tumor genome-wide sequencing. They presented their findings at the International Association for the Study of Lung Cancer (IASCL) 2020 World Conference on Lung Cancer in Singapore (WCLC), held in virtual format in January 2021 (Abstract FP12.12). In brief, those who had lung cancer and never smoked seemed to have a lower tumor mutation burden than a control cohort of patients with a history of smoking.

“Lung cancer cases in never-smokers are more common among women and are three- to fourfold more common among Asian women,” Dr. Moorthi said in an IASLC press release. “Despite this, the majority of tumor genome-wide sequencing efforts in lung cancer have been focused on patient cohorts with a smoking history.”

Using tumor tissue of patients with lung cancer and a never-smoking background from the Women’s Health Initiative, the researchers performed whole-exome sequencing on 75 tumor-normal pairs. Via the use of a consensus dual-caller and filtering methodology, mutations were identified for the cohort, and variants were analyzed to determine significant genes' mutations.

The mutational analysis showed an enrichment of known oncogenes such as KRAS, EGFR, and TP53, along with mutations in STK11. Novel copy number alterations and structural variants were also discovered from this sample. Compared with a cohort of patients with a history of smoking, this nonsmoking cohort had a lower tumor mutational burden. Furthermore, these specific gene mutations were found in other patients with lung cancer who were never-smokers, suggesting an opportunity for therapeutic targeting in the future.

Disclosure: For full disclosures of the study authors, visit wclc2020.iaslc.org.



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