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

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 Razavi, Helena A. Yu, Jorge S. Reis-Filho, Daniel Gomez, Nikolaus Schultz and Luke R. G. Pike ()
Additional contact information
Anna Skakodub: Memorial Sloan Kettering Cancer Center
Henry Walch: 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
Bob T. Li: 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
Helena A. Yu: Memorial Sloan Kettering Cancer Center
Jorge S. Reis-Filho: Memorial Sloan Kettering Cancer Center
Daniel Gomez: Memorial Sloan Kettering Cancer Center
Nikolaus Schultz: Memorial Sloan Kettering Cancer Center
Luke R. G. Pike: Memorial Sloan Kettering Cancer Center

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-40793-x

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