Genomic landscape of lung adenocarcinoma in East Asians.

Adenocarcinoma of Lung / etiology Aged Asian People / genetics Cohort Studies DNA Copy Number Variations ErbB Receptors / genetics Exome Female Gene Expression Profiling Humans Lung Neoplasms / etiology Male Middle Aged Mutation Proto-Oncogene Proteins p21(ras) / genetics Singapore Tumor Suppressor Protein p53 / genetics

Journal

Nature genetics

ISSN: 1546-1718

Titre abrégé: Nat Genet

Pays: United States

ID NLM: 9216904

Informations de publication

Date de publication:
02 2020

Historique:

received: 08 01 2019

accepted: 12 12 2019

pubmed: 6 2 2020

medline: 14 4 2020

entrez: 5 2 2020

Statut: ppublish

Résumé

Lung cancer is the world's leading cause of cancer death and shows strong ancestry disparities. By sequencing and assembling a large genomic and transcriptomic dataset of lung adenocarcinoma (LUAD) in individuals of East Asian ancestry (EAS; n = 305), we found that East Asian LUADs had more stable genomes characterized by fewer mutations and fewer copy number alterations than LUADs from individuals of European ancestry. This difference is much stronger in smokers as compared to nonsmokers. Transcriptomic clustering identified a new EAS-specific LUAD subgroup with a less complex genomic profile and upregulated immune-related genes, allowing the possibility of immunotherapy-based approaches. Integrative analysis across clinical and molecular features showed the importance of molecular phenotypes in patient prognostic stratification. EAS LUADs had better prediction accuracy than those of European ancestry, potentially due to their less complex genomic architecture. This study elucidated a comprehensive genomic landscape of EAS LUADs and highlighted important ancestry differences between the two cohorts.

Identifiants

DOI: 10.1038/s41588-019-0569-6 PMID: 32015526

pubmed: 32015526

doi: 10.1038/s41588-019-0569-6

pii: 10.1038/s41588-019-0569-6

doi:

Substances chimiques

KRAS protein, human 0

TP53 protein, human 0

Tumor Suppressor Protein p53 0

EGFR protein, human EC 2.7.10.1

ErbB Receptors EC 2.7.10.1

Proto-Oncogene Proteins p21(ras) EC 3.6.5.2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

177-186

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