Tracing Oncogene Rearrangements in the Mutational History of Lung Adenocarcinoma.
© KATERYNA KON/SCIENCE PHOTO LIBRARY/Getty
Cancer-causing fusions between genes often arise early in life and can trigger lung cancer many decades later, even among people who never smoke.
A team co-led by researchers from the Korea Advanced Institute of Science and Technology (KAIST) sequenced the DNA of lung tumors from 138 patients.
Among smokers, they found that the genomes were full of simple DNA substitutions, insertions and deletions, most of which were acquired in later life.
In contrast, among non-smokers they observed complex genomic rearrangements, most of which had originated in childhood or adolescence and sat dormant for several decades until further mutations accumulated to prompt cancer progression.
These instigating gene fusions may be therapeutically targetable to prevent or treat lung cancer in non-smokers. They might also be more widespread in the body and underpin other types of cancer, a possibility that the KAIST team is now exploring.
- Cell 177, 1842–1857 (2019). doi: 10.1016/j.cell.2019.05.013