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Genomic analysis and clinical correlations of non-small cell lung cancer brain metastasis

Author

Listed:
  • Anna Skakodub

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Henry Walch

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Kathryn R. Tringale

    (Memorial Sloan Kettering Cancer Center)

  • Jordan Eichholz

    (Memorial Sloan Kettering Cancer Center)

  • Brandon S. Imber

    (Memorial Sloan Kettering Cancer Center)

  • Harish N. Vasudevan

    (University of California San Francisco
    University of California)

  • Bob T. Li

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Nelson S. Moss

    (Memorial Sloan Kettering Cancer Center)

  • Kenny Kwok Hei Yu

    (Memorial Sloan Kettering Cancer Center)

  • Boris A. Mueller

    (Memorial Sloan Kettering Cancer Center)

  • Simon Powell

    (Memorial Sloan Kettering Cancer Center)

  • Pedram Razavi

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Helena A. Yu

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Jorge S. Reis-Filho

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Daniel Gomez

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Nikolaus Schultz

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Luke R. G. Pike

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

Abstract

Up to 50% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), yet the study of BM genomics has been limited by tissue access, incomplete clinical data, and a lack of comparison with paired extracranial specimens. Here we report a cohort of 233 patients with resected and sequenced (MSK-IMPACT) NSCLC BM and comprehensive clinical data. With matched samples (47 primary tumor, 42 extracranial metastatic), we show CDKN2A/B deletions and cell cycle pathway alterations to be enriched in the BM samples. Meaningful clinico-genomic correlations are noted, namely EGFR alterations in leptomeningeal disease (LMD) and MYC amplifications in multifocal regional brain progression. Patients who developed early LMD frequently have had uncommon, multiple, and persistently detectable EGFR driver mutations. The distinct mutational patterns identified in BM specimens compared to other tissue sites suggest specific biologic underpinnings of intracranial progression.

Suggested Citation

  • Anna Skakodub & Henry Walch & Kathryn R. Tringale & Jordan Eichholz & Brandon S. Imber & Harish N. Vasudevan & Bob T. Li & Nelson S. Moss & Kenny Kwok Hei Yu & Boris A. Mueller & Simon Powell & Pedram, 2023. "Genomic analysis and clinical correlations of non-small cell lung cancer brain metastasis," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40793-x
    DOI: 10.1038/s41467-023-40793-x
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    References listed on IDEAS

    as
    1. Leticia De Mattos-Arruda & Regina Mayor & Charlotte K. Y. Ng & Britta Weigelt & Francisco Martínez-Ricarte & Davis Torrejon & Mafalda Oliveira & Alexandra Arias & Carolina Raventos & Jiabin Tang & Ele, 2015. "Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma," Nature Communications, Nature, vol. 6(1), pages 1-6, December.
    2. Qi Zhang & Rober Abdo & Cristiana Iosef & Tomonori Kaneko & Matthew Cecchini & Victor K. Han & Shawn Shun-Cheng Li, 2022. "The spatial transcriptomic landscape of non-small cell lung cancer brain metastasis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
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