Hi everyone, I'm Annette Salomonsson from Lund University in Sweden, presenting the project, a nationwide population-based mapping of mutations and gene fusions in lung cancer among nevus smokers. I have no disclosures. 10-15% of all lung cancer patients have never smoked. Studies indicate that these patients have certain molecular and clinical features and often harbor targetable driver alterations. However, the nationwide population-based prevalence and spectrum of mutations and gene fusions among Swedish nevus smokers have not yet been investigated. Through the National Lung Cancer Registry, we identified nevus smokers that underwent lung cancer surgery in Sweden during a 10-year period. Archived surgically resected tumor material was retrieved and a thoracic pathologist reviewed the histology and selected representative tumor tissue blocks. Patients' medical charts were reviewed to verify smoking status and to assemble clinical data. DNA and RNA was extracted from representative specimens selected by the thoracic pathologist. We used the nonostring encounter element assay for detection of gene fusions and methoxone-14 skipping. The fusions included in the assay were ALK, RET, PROSVAN, ENERGY WAND, and ENTRAC. For mutation analysis, we used a 15 or 26 gene exome-focused NGS panel. Through the National Lung Cancer Registry, we identified 545 cases. Archived material was missing for 58 cases. After reviewing the histology, 17 cases were found to have a diagnosis other than primary lung carcinoma. After reviewing patients' medical charts, 31 were found to have a history of smoking, which gave us 439 tumors that could be included in the study. Out of these, 417 samples have successfully been analyzed with nonostring. So far, 138 samples have been analyzed with both nonostring and NGS. So results from the nonostring analysis, 417 cases have successfully been analyzed by nonostring for detection of gene fusions and methoxone-14 skipping. Alterations were detected in 25 percent of the cases. The most common alterations were methoxone-14 skipping, which is the blue part in the pie chart, ALK fusions, which is the orange part, and RET fusions, which is the gray part. But also NRG1, ROS1, and N-TRAC fusions were detected. So now results from both the nonostring and the NGS analysis. So far, 138 samples have successfully been analyzed with both nonostring and NGS. 22 percent of these cases had gene fusions or methoxone-14 skipping, which is the blue part in the pie chart. 43 percent of the cases had EGFR mutations indexed on 19 or 21, which is the orange part. One patient had a BRAF V600E mutation. 19 percent had mutations in potentially targetable genes, such as other EGFR mutations, or mutations in KRAS, HER2, or BRAF mutations other than V600E, which is the yellow part. So only 15 percent of the samples, which is the light blue part, had no findings with nonostring or NGS. Take-home message. A high frequency of oncogene drivers was detected among Naborsmukers. Among the first 138 samples that have successfully been analyzed with both nonostring and NGS, 85 percent of the samples had alterations in targetable or potentially targetable genes. I would like to acknowledge all authors of this work. Thank you for listening.

lung cancer

gene fusions

mutation analysis

targetable genes

never smokers