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Spatiotemporal genomic analysis reveals distinct molecular features in recurrent stage I non-small cell lung cancers

Chen, Kezhong; Yang, Airong; Carbone, David P; Kanu, Nnennaya; Liu, Ke; Wang, Ruiru; Nie, Yuntao; ... Wang, Jun; + view all (2022) Spatiotemporal genomic analysis reveals distinct molecular features in recurrent stage I non-small cell lung cancers. Cell Reports , 40 (2) , Article 111047. 10.1016/j.celrep.2022.111047. Green open access

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Abstract

Stage I non-small cell lung cancer (NSCLC) presents diverse outcomes. To identify molecular features leading to tumor recurrence in early-stage NSCLC, we perform multiregional whole-exome sequencing (WES), RNA sequencing, and plasma-targeted circulating tumor DNA (ctDNA) detection analysis between recurrent and recurrent-free stage I NSCLC patients (CHN-P cohort) who had undergone R0 resection with a median 5-year follow-up time. Integrated analysis indicates that the multidimensional clinical and genomic model can stratify the prognosis of stage I NSCLC in both CHN-P and EUR-T cohorts and correlates with positive pre-surgical deep next generation sequencing (NGS) ctDNA detection. Increased genomic instability related to DNA interstrand crosslinks and double-strand break repair processes is significantly associated with early tumor relapse. This study reveals important molecular insights into stage I NSCLC and may inform clinical postoperative treatment and follow-up strategies.

Type: Article
Title: Spatiotemporal genomic analysis reveals distinct molecular features in recurrent stage I non-small cell lung cancers
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2022.111047
Publisher version: https://doi.org/10.1016/j.celrep.2022.111047
Language: English
Additional information: © 2022 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Non-small cell lung cancer, heterogeneity, multiregion, genomic, early stage, surgery, disease-free survival, circulating tumor DNA, genome instability, DNA damage repair
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10152423
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