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CHD5 gene variant predicts leptomeningeal metastasis after surgical resection of brain metastases of breast cancer

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Leptomeningeal metastasis (LM) is a complication of surgery for brain metastasis and is a risk factor of poor prognosis. The risk of LM is particularly high after surgery for a breast cancer metastasis to the brain. If the risk of LM after surgical resection for a brain metastasis were predictable, appropriate adjuvant therapy could be administered to individual patients to improve their prognosis. The present study aimed to reveal the genetic characteristics of brain metastases as means of predicting LM in breast cancer patients.


Ten patients with brain metastases of breast cancer presented LM after surgical resection were analyzed by whole-exome sequencing.


A chromodomain-helicase-DNA-binding protein 5 (CHD5) gene alteration was detected in nine cases (90%), including a nonsynonymous variant in four cases and copy number deletion in five cases. CHD5 protein expression was lost in nine cases and had decreased in one case. The frequency of CHD5 gene alteration in brain metastases with LM was significantly higher than in primary breast cancer (2.3%) or in brain metastases of breast cancer (0%) (p < 0.0001).


These results suggested that the CHD5 gene alteration was associated with LM after surgical resection of breast cancer brain metastases. Searching for the gene alteration might predict the LM risk after surgical resection.

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Data Availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

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We are grateful to the patients for donating their tissue to research.


This study was supported by the Clinical Research Fund of the Tokyo Metropolitan Government (R030303007).

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Authors and Affiliations



Designed and performed the study: R.O. Sample correction: R.O., R.Y., H.Y. Analysis and interpretation of whole exome sequence data: D.S., R.O. Manuscript: R.O., D.S. Review and discussion of the manuscript: all the authors.

Corresponding author

Correspondence to Ryohei Otani.

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Ethics approval

The present study was approved by the ethics committee at Tokyo Metropolitan Komagome Hospital (No. 2631).

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Written informed consent was obtained from all individual participants included in the study.

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Patients signed informed consent regarding publishing their data.

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The authors declare that they have no competing interests.

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Supplementary Table S1. All pathogenic variants detected in ten cases of breast cancer-related brain metastases with leptomeningeal metastasis after surgical resection. VAF, Variant allele frequency.


Supplementary Table S2. Frequency of CHD5 gene variants in brain metastases and primary lesions of various cancer types other than breast cancer in the TCGA data.


Supplementary Figure S1. Immunohistochemical staining of the CHD5 protein in all the samples of breast cancer-related brain metastasis with leptomeningeal metastasis in the present study. The positive control is also shown.

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Otani, R., Sadato, D., Yamada, R. et al. CHD5 gene variant predicts leptomeningeal metastasis after surgical resection of brain metastases of breast cancer. J Neurooncol 163, 657–662 (2023).

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