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Sequencing 305 lung adenocarcinomas from East Asian patients showed that the same cancer in a different population has a calmer genome, far more of the one mutation that has a good pill, and an immune-rich subgroup that nobody had described.
A genomic and transcriptomic dataset of 305 lung adenocarcinomas from individuals of East Asian ancestry was assembled and compared with European-ancestry cohorts. East Asian tumours had more stable genomes, with fewer mutations and fewer copy-number alterations, and the difference was much stronger in smokers than in non-smokers. Transcriptomic clustering identified an East Asian-specific subgroup with a less complex genomic profile and upregulated immune-related genes, raising the possibility of immunotherapy-based approaches. Integrative analysis across clinical and molecular features showed the importance of molecular phenotypes in prognostic stratification, and prediction accuracy was better in the East Asian cohort than in the European-ancestry one, potentially because of the simpler genomic architecture.
It shows that the driver frequencies quoted in Western guidelines are population statistics rather than facts about the disease, which matters for how many patients anywhere are expected to benefit from a given medicine.
Shares Copy number alteration (CNA), EGFR exon 19 deletion, EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M), Nature Genetics.
Shares KEAP1, STK11, Non-small cell lung cancer (KEGG map), Driver mutation.
Shares KEAP1, STK11, Non-small cell lung cancer (KEGG map), Driver mutation.
Shares Nature Genetics, Receptor tyrosine kinase activation, TP53, EGFR.
Shares EGFR L858R, EGFR exon 19 deletion, EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M), Receptor tyrosine kinase activation.
Shares EGFR L858R, EGFR exon 19 deletion, EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M), Non-small cell lung cancer (KEGG map).
Shares Nature Genetics, Non-small cell lung cancer (KEGG map), Driver mutation, Whole-exome & whole-genome sequencing.
Shares Copy number alteration (CNA), KEAP1, Non-small cell lung cancer (KEGG map), Driver mutation.