New research from institutions in Singapore and China have identified genetic differences that occur in lung adenocarcinomas in East Asians and Europeans. Published in Nature Genetics, the researchers found that lung adenocarcinomas had more stable genomes in East Asians than in Europeans, and a stronger difference in smokers compared to non-smokers.

Lung adenocarcinoma is a form of non-small cell lung cancer, the most common type of lung cancer (80%) of which 50% of these are adenocarcinomas. They are most common in women, Asians, and people under the age of 45, and lung cancers form one of the most deadliest types of cancer worldwide.

This new research involved 213 tumours from Chinese lung cancer patients that underwent exome and transcriptome sequencing, along with another 92 Chinese patients from a BGI cohort. The researchers then compared this with 305 European data in the Cancer Genome Atlas to find differences in tumour mutational burden (TMB). This is a measurement of mutations carried by tumour cells and is a predictive biomarker that can evaluate how well the tumour will respond to immunotherapy.

Lung adenocarcinomas in East Asians were found to have fewer genetic alterations than Europeans, with an average TMB of 2.04 per Mb compared with 5.08 per Mb. In individuals who smoked, these TMB averages were different but were still lower in East Asian patients than in Europeans. Different driver mutations were also identified and at different frequencies between the two groups.

Transcriptome analysis revealed some findings that could identify which therapies would work best for different patients. They found that two out of three cancer sub-clusters in East Asians were similar to terminal respiratory unit and proximal inflammatory sub-clusters seen in Europeans before, and the third sub-cluster was only found in East Asian patients. Survival rate predictions were more accurate in East Asian patients, and could have been because of the more stable genomes in East Asians compared to Europeans.

This study highlighted the importance of ancestry in the genomic landscape of adenocarcinomas from these two cohorts, and could help in determining which therapies could be best for different patients.