Genomic Landscape and Actionable Mutations of Brain Metastases derived from Non-Small Cell Lung Cancer: a Systematic Review

Lily Andrews; Zak Thornton; Ruqiya Saleh; Sarah Dawson; Susan C Short; Richard S Daly; Julian P T Higgins; Philippa Davies; Kathreena M Kurian

doi:10.1093/noajnl/vdad145

Genomic Landscape and Actionable Mutations of Brain Metastases derived from Non-Small Cell Lung Cancer: a Systematic Review

Lily Andrews^*, Zak Thornton, Ruqiya Saleh, Sarah Dawson, Susan C Short, Richard S Daly, Julian P T Higgins, Philippa Davies, Kathreena M Kurian^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

Abstract

Background
Brain metastases derived from non–small cell lung cancer (NSCLC) represent a significant clinical problem. We aim to characterize the genomic landscape of brain metastases derived from NSCLC and assess clinical actionability.

Methods
We searched Embase, MEDLINE, Web of Science, and BIOSIS from inception to 18/19 May 2022. We extracted information on patient demographics, smoking status, genomic data, matched primary NSCLC, and programmed cell death ligand 1 expression.

Results
We found 72 included papers and data on 2346 patients. The most frequently mutated genes from our data were EGFR (n = 559), TP53 (n = 331), KRAS (n = 328), CDKN2A (n = 97), and STK11 (n = 72). Common missense mutations included EGFR L858R (n = 80) and KRAS G12C (n = 17). Brain metastases of ever versus never smokers had differing missense mutations in TP53 and EGFR, except for L858R and T790M in EGFR, which were seen in both subgroups. Of the top 10 frequently mutated genes that had primary NSCLC data, we found 37% of the specific mutations assessed to be discordant between the primary NSCLC and brain metastases.

Conclusions
To our knowledge, this is the first systematic review to describe the genomic landscape of brain metastases derived from NSCLC. These results provide a comprehensive outline of frequently mutated genes and missense mutations that could be clinically actionable. These data also provide evidence of differing genomic landscapes between ever versus never smokers and primary NSCLC compared to the BM. This information could have important consequences for the selection and development of targeted drugs for these patients.

Original language	English
Article number	vdad145
Number of pages	15
Journal	Neuro-Oncology Advances
Volume	5
Issue number	1
Early online date	24 Nov 2023
DOIs	https://doi.org/10.1093/noajnl/vdad145
Publication status	Published - 21 Dec 2023

Bibliographical note

Funding Information: L.J.A. and K.M.K. are funded by Cancer Research UK (grant number C30758/A29791); Z.A.T. is funded by Southmead Hospital Charitable Funds: Brain tumour bank and research fund 8036. This work was supported by Cancer Research UK [grant number C18281/A29019 and C18281/A30905]. K.M.K. is funded by Innovate [grant number 10027624]. J.P.T.H. is a National Institute for Health and Care Research (NIHR) Senior Investigator (NIHR203807). The views expressed in this article are those of the author(s) and not necessarily those of the NIHR, or the Department of Health and Social Care.

Publisher Copyright: © The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

Research Groups and Themes

ICEP

Keywords

Brain metastases
non-small cell lung cancer
genomics
actionable mutations

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1093/noajnl/vdad145Licence: CC BY

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Persistent link

8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival
Martin, R. M. (Principal Investigator)
1/10/20 → 30/09/25
Project: Research

Cite this

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title = "Genomic Landscape and Actionable Mutations of Brain Metastases derived from Non-Small Cell Lung Cancer: a Systematic Review",

abstract = "BackgroundBrain metastases derived from non–small cell lung cancer (NSCLC) represent a significant clinical problem. We aim to characterize the genomic landscape of brain metastases derived from NSCLC and assess clinical actionability.MethodsWe searched Embase, MEDLINE, Web of Science, and BIOSIS from inception to 18/19 May 2022. We extracted information on patient demographics, smoking status, genomic data, matched primary NSCLC, and programmed cell death ligand 1 expression.ResultsWe found 72 included papers and data on 2346 patients. The most frequently mutated genes from our data were EGFR (n = 559), TP53 (n = 331), KRAS (n = 328), CDKN2A (n = 97), and STK11 (n = 72). Common missense mutations included EGFR L858R (n = 80) and KRAS G12C (n = 17). Brain metastases of ever versus never smokers had differing missense mutations in TP53 and EGFR, except for L858R and T790M in EGFR, which were seen in both subgroups. Of the top 10 frequently mutated genes that had primary NSCLC data, we found 37% of the specific mutations assessed to be discordant between the primary NSCLC and brain metastases.ConclusionsTo our knowledge, this is the first systematic review to describe the genomic landscape of brain metastases derived from NSCLC. These results provide a comprehensive outline of frequently mutated genes and missense mutations that could be clinically actionable. These data also provide evidence of differing genomic landscapes between ever versus never smokers and primary NSCLC compared to the BM. This information could have important consequences for the selection and development of targeted drugs for these patients.",

keywords = "Brain metastases, non-small cell lung cancer, genomics, actionable mutations",

author = "Lily Andrews and Zak Thornton and Ruqiya Saleh and Sarah Dawson and Short, {Susan C} and Daly, {Richard S} and Higgins, {Julian P T} and Philippa Davies and Kurian, {Kathreena M}",

note = "Funding Information: L.J.A. and K.M.K. are funded by Cancer Research UK (grant number C30758/A29791); Z.A.T. is funded by Southmead Hospital Charitable Funds: Brain tumour bank and research fund 8036. This work was supported by Cancer Research UK [grant number C18281/A29019 and C18281/A30905]. K.M.K. is funded by Innovate [grant number 10027624]. J.P.T.H. is a National Institute for Health and Care Research (NIHR) Senior Investigator (NIHR203807). The views expressed in this article are those of the author(s) and not necessarily those of the NIHR, or the Department of Health and Social Care. Publisher Copyright: {\textcopyright} The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.",

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doi = "10.1093/noajnl/vdad145",

language = "English",

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TY - JOUR

T1 - Genomic Landscape and Actionable Mutations of Brain Metastases derived from Non-Small Cell Lung Cancer

T2 - a Systematic Review

AU - Andrews, Lily

AU - Thornton, Zak

AU - Saleh, Ruqiya

AU - Dawson, Sarah

AU - Short, Susan C

AU - Daly, Richard S

AU - Higgins, Julian P T

AU - Davies, Philippa

AU - Kurian, Kathreena M

N1 - Funding Information: L.J.A. and K.M.K. are funded by Cancer Research UK (grant number C30758/A29791); Z.A.T. is funded by Southmead Hospital Charitable Funds: Brain tumour bank and research fund 8036. This work was supported by Cancer Research UK [grant number C18281/A29019 and C18281/A30905]. K.M.K. is funded by Innovate [grant number 10027624]. J.P.T.H. is a National Institute for Health and Care Research (NIHR) Senior Investigator (NIHR203807). The views expressed in this article are those of the author(s) and not necessarily those of the NIHR, or the Department of Health and Social Care. Publisher Copyright: © The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

PY - 2023/12/21

Y1 - 2023/12/21

N2 - BackgroundBrain metastases derived from non–small cell lung cancer (NSCLC) represent a significant clinical problem. We aim to characterize the genomic landscape of brain metastases derived from NSCLC and assess clinical actionability.MethodsWe searched Embase, MEDLINE, Web of Science, and BIOSIS from inception to 18/19 May 2022. We extracted information on patient demographics, smoking status, genomic data, matched primary NSCLC, and programmed cell death ligand 1 expression.ResultsWe found 72 included papers and data on 2346 patients. The most frequently mutated genes from our data were EGFR (n = 559), TP53 (n = 331), KRAS (n = 328), CDKN2A (n = 97), and STK11 (n = 72). Common missense mutations included EGFR L858R (n = 80) and KRAS G12C (n = 17). Brain metastases of ever versus never smokers had differing missense mutations in TP53 and EGFR, except for L858R and T790M in EGFR, which were seen in both subgroups. Of the top 10 frequently mutated genes that had primary NSCLC data, we found 37% of the specific mutations assessed to be discordant between the primary NSCLC and brain metastases.ConclusionsTo our knowledge, this is the first systematic review to describe the genomic landscape of brain metastases derived from NSCLC. These results provide a comprehensive outline of frequently mutated genes and missense mutations that could be clinically actionable. These data also provide evidence of differing genomic landscapes between ever versus never smokers and primary NSCLC compared to the BM. This information could have important consequences for the selection and development of targeted drugs for these patients.

AB - BackgroundBrain metastases derived from non–small cell lung cancer (NSCLC) represent a significant clinical problem. We aim to characterize the genomic landscape of brain metastases derived from NSCLC and assess clinical actionability.MethodsWe searched Embase, MEDLINE, Web of Science, and BIOSIS from inception to 18/19 May 2022. We extracted information on patient demographics, smoking status, genomic data, matched primary NSCLC, and programmed cell death ligand 1 expression.ResultsWe found 72 included papers and data on 2346 patients. The most frequently mutated genes from our data were EGFR (n = 559), TP53 (n = 331), KRAS (n = 328), CDKN2A (n = 97), and STK11 (n = 72). Common missense mutations included EGFR L858R (n = 80) and KRAS G12C (n = 17). Brain metastases of ever versus never smokers had differing missense mutations in TP53 and EGFR, except for L858R and T790M in EGFR, which were seen in both subgroups. Of the top 10 frequently mutated genes that had primary NSCLC data, we found 37% of the specific mutations assessed to be discordant between the primary NSCLC and brain metastases.ConclusionsTo our knowledge, this is the first systematic review to describe the genomic landscape of brain metastases derived from NSCLC. These results provide a comprehensive outline of frequently mutated genes and missense mutations that could be clinically actionable. These data also provide evidence of differing genomic landscapes between ever versus never smokers and primary NSCLC compared to the BM. This information could have important consequences for the selection and development of targeted drugs for these patients.

KW - Brain metastases

KW - non-small cell lung cancer

KW - genomics

KW - actionable mutations

U2 - 10.1093/noajnl/vdad145

DO - 10.1093/noajnl/vdad145

M3 - Article (Academic Journal)

C2 - 38130901

SN - 2632-2498

VL - 5

JO - Neuro-Oncology Advances

JF - Neuro-Oncology Advances

IS - 1

M1 - vdad145

ER -

Genomic Landscape and Actionable Mutations of Brain Metastases derived from Non-Small Cell Lung Cancer: a Systematic Review

Abstract

Bibliographical note

Research Groups and Themes

Keywords

UN SDGs

Access to Document

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Projects

8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival

Cite this