Genomic analysis and clinical correlations of non-small cell lung cancer brain metastasis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 08 2023
17 08 2023
Historique:
received:
28
03
2023
accepted:
10
08
2023
medline:
21
8
2023
pubmed:
18
8
2023
entrez:
17
8
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37591896
doi: 10.1038/s41467-023-40793-x
pii: 10.1038/s41467-023-40793-x
pmc: PMC10435547
doi:
Substances chimiques
ErbB Receptors
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4980Informations de copyright
© 2023. Springer Nature Limited.
Références
Nat Commun. 2015 Nov 10;6:8839
pubmed: 26554728
JCO Precis Oncol. 2017 Jul;2017:
pubmed: 28890946
CA Cancer J Clin. 2018 Jan;68(1):7-30
pubmed: 29313949
J Thorac Oncol. 2016 Nov;11(11):1962-1969
pubmed: 27539328
Oncotarget. 2018 Apr 17;9(29):20617-20630
pubmed: 29755676
Cancer Discov. 2020 Jan;10(1):86-103
pubmed: 31601552
Nat Commun. 2022 Oct 10;13(1):5983
pubmed: 36216799
Ann Transl Med. 2021 Oct;9(19):1506
pubmed: 34805368
J Thorac Oncol. 2023 Apr;18(4):463-475
pubmed: 36494075
Immunology. 2019 Dec;158(4):255-266
pubmed: 31509607
Sci Signal. 2013 Apr 02;6(269):pl1
pubmed: 23550210
J Mol Diagn. 2015 May;17(3):251-64
pubmed: 25801821
Neuro Oncol. 2017 Oct 19;19(11):1511-1521
pubmed: 28444227
JCO Precis Oncol. 2019 Dec;3:1-13
pubmed: 35100709
Lung Cancer. 2019 Jan;127:1-5
pubmed: 30642536
Nucleic Acids Res. 2016 Sep 19;44(16):e131
pubmed: 27270079
Cancer Discov. 2015 Nov;5(11):1164-1177
pubmed: 26410082
Cell Rep Med. 2023 Jan 17;4(1):100900
pubmed: 36652909
Hered Cancer Clin Pract. 2021 Mar 25;19(1):21
pubmed: 33766116
Nat Genet. 2018 Aug;50(8):1189-1195
pubmed: 30013179
Genes Chromosomes Cancer. 2017 Jul;56(7):559-569
pubmed: 28379620
Science. 2020 Jul 17;369(6501):276-282
pubmed: 32675368
PLoS One. 2013 Nov 12;8(11):e78641
pubmed: 24265703
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
J Clin Pathol. 2022 Jun;75(6):361-364
pubmed: 34996754
Clin Cancer Res. 2015 Jul 1;21(13):2905-10
pubmed: 25941111
Cell. 2022 Feb 3;185(3):563-575.e11
pubmed: 35120664
Oncologist. 2022 Oct 1;27(10):839-848
pubmed: 35598205
Cell. 2018 Apr 5;173(2):321-337.e10
pubmed: 29625050
Nat Genet. 2020 Apr;52(4):371-377
pubmed: 32203465