ArticleOncogene2019
Deep multi-region whole-genome sequencing reveals heterogeneity and gene-by-environment interactions in treatment-naive, metastatic lung cancer.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Examining the role of extrachromosomal DNA in lung cancer.Journal of the National Cancer Institute · 2026Article
- Article
- Panorama of Chromosomal Instability in Lung Cancer.medRxiv : the preprint server for health sciences · 2025Article
- Lung cancer biobanking in Australia: challenges and future directions.The Medical journal of Australia · 2025Article
- APOBEC affects tumor evolution and age at onset of lung cancer in smokers.Nature communications · 2025Article
- Spatial deconvolution from bulk DNA methylation profiles determines intratumoral epigenetic heterogeneity.Cell & bioscience · 2025Article
- THOR: a TMB heterogeneity-adaptive optimization model predicts immunotherapy response using clonal genomic features in group-structured data.Briefings in bioinformatics · 2024Article
- From Genomic Exploration to Personalized Treatment: Next-Generation Sequencing in Oncology.Current issues in molecular biology · 2024Review
- CRUX, a platform for visualising, exploring and analysing cancer genome cohort data.NAR genomics and bioinformatics · 2024Article
- High expression of transcription factor POU2F1 confers improved survival on smokers with lung adenocarcinoma: a retrospective study of two cohorts.Translational lung cancer research · 2023Article
- Discrepancies in tumor mutation burden reporting from sequential endobronchial ultrasound transbronchial needle aspiration samples within single lymph node stations - brief report.Frontiers in oncology · 2023Article
- Heterogeneity of tumour mutational burden in metastatic NSCLC demonstrated by endobronchial ultrasound sampling.Frontiers in oncology · 2023Article
- Editorial: Overcoming drug relapse and therapy resistance in NSCLC.Frontiers in oncology · 2023Article
- A phylogenetic approach to study the evolution of somatic mutational processes in cancer.Communications biology · 2022Article
- Immunogenomic intertumor heterogeneity across primary and metastatic sites in a patient with lung adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Identification of neoantigens for individualized therapeutic cancer vaccines.Nature reviews. Drug discovery · 2022Review
- Homologous Recombination Deficiency in Ovarian, Breast, Colorectal, Pancreatic, Non-Small Cell Lung and Prostate Cancers, and the Mechanisms of Resistance to PARP Inhibitors.Frontiers in oncology · 2022Review
- CometChip analysis of human primary lymphocytes enables quantification of inter-individual differences in the kinetics of repair of oxidative DNA damage.Free radical biology & medicine · 2021Article
- Integrating endobronchial ultrasound bronchoscopy with molecular testing of immunotherapy biomarkers in non-small cell lung cancer.Translational lung cancer research · 2021Review
- Integrative reconstruction of cancer genome karyotypes using InfoGenomeR.Nature communications · 2021Article
Corrections and comments
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Authors and funding
28 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our understanding of genomic heterogeneity in lung cancer is largely based on the analysis of early-stage surgical specimens. Here we used endoscopic sampling of paired primary and intrathoracic metastatic tumors from 11 lung cancer patients to map genomic heterogeneity inoperable lung cancer with deep whole-genome sequencing. Intra-patient heterogeneity in driver or targetable mutations was predominantly in the form of copy number gain. Private mutation signatures, including patterns consistent with defects in homologous recombination, were highly variable both within and between patients. Irrespective of histotype, we observed a smaller than expected number of private mutations, suggesting that ancestral clones accumulated large mutation burdens immediately prior to metastasis. Single-region whole-genome sequencing of from 20 patients showed that tumors in ever-smokers with the strongest tobacco signatures were associated with germline variants in genes implicated in the repair of cigarette-induced DNA damage. Our results suggest that lung cancer precursors in ever-smokers accumulate large numbers of mutations prior to the formation of frank malignancy followed by rapid metastatic spread. In advanced lung cancer, germline variants in DNA repair genes may interact with the airway environment to influence the pattern of founder mutations, whereas similar interactions with the tumor microenvironment may play a role in the acquisition of mutations following metastasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.