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At the same time, the number and nature of driver mutations differed between tumors from East Asian and European patients. In East Asian patients, alterations affecting the EGFR, TP53, and KRAS genes were the most common driver mutations and nonsmokers had an average 2.08 driver mutations, as compared to an average 2.65 driver mutations among European nonsmokers. Additionally, East Asian patients had fewer copy number variations.
Together, these findings indicated that lung adenocarcinomas from East Asian patients typically have fewer genomic alterations and less complex genomic profiles than those from European patients.
By analyzing the transcriptomic profiles of the tumor samples, the researchers teased out three different lung cancer subclusters. Two of these were similar to the terminal respiratory unit (TRU) and proximal inflammatory subclusters previously found in European patients, but the third was specific to East Asians. That subcluster, dubbed TRU-I, was marked by the upregulation of inflammation-associated genes and increased immune infiltration. This phenotype could help identify patients who might be more likely to benefit from immunotherapy or immune checkpoint blockade treatment, the researchers wrote.
While they found that patients’ clinical features could predict their outcomes, they noted that genomic features could also predict patient survival. These predictions were more accurate for East Asian than European patients, which the researchers attributed to their more stable tumor genomes.
“This study elucidated a comprehensive genomic landscape of EAS [lung adenocarcinomas] and highlighted important ancestry differences between the two cohorts,” the researchers wrote in their paper.