Cancer Res Treat.  2024 Apr;56(2):665-674. 10.4143/crt.2023.864.

Case Series of Soft Tissue Sarcoma Patients with Brain Metastasis with Implications from Genomic and Transcriptomic Analysis

• Park C
• Kim R
• Choi J
• Kim M
• Kim TM
• Han I
• Kim JI
• Kim HS

• KMID: 2554355
• DOI: http://doi.org/10.4143/crt.2023.864

Abstract

Purpose
Brain metastasis rarely occurs in soft tissue sarcoma (STS). Here, we present five cases of STS with brain metastases with genetic profiles.
Materials and Methods
We included five patients from Seoul National University Hospital who were diagnosed with STS with metastasis to the brain. Tissue from the brain metastasis along with that from the primary site or other metastases were used for DNA and RNA sequencing to identify genetic profiles. Gene expression profiles were compared with sarcoma samples from The Cancer Genome Atlas.
Results
The overall survival after diagnosis of brain metastasis ranged from 2.2 to 34.3 months. Comparison of mutational profiles between brain metastases and matched primary or other metastatic samples showed similar profiles. In two patients, copy number variation profiles between brain metastasis and other tumors showed several differences including MYCL, JUN, MYC, and DDR2 amplification. Gene ontology analysis showed that the group of genes significantly highly expressed in the brain metastasis samples was enriched in the G-protein coupled receptor activity, structural constituent of chromatin, protein heterodimerization activity, and binding of DNA, RNA, and protein. Gene set enrichment analysis showed enrichment in the pathway of neuroactive ligand-receptor interaction and systemic lupus erythematosus.
Conclusion
The five patients had variable ranges of clinical courses and outcomes. Genomic and transcriptomic analysis of STS with brain metastasis implicates possible involvement of complex expression modification and epigenetic changes rather than the addition of single driver gene alteration.

Keyword

Sarcoma; Brain neoplasms; Genomics; Transcriptomics

Figure

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  Fig. 1. Genetic alterations in patients C and D. (A) Copy number variation heatmap of whole chromosomes aligned by each patient’s tumor progression timeline for patients C and D. Regions with a copy number of 2 or 3 are colored white on the scale provided to the left. Indicated genes above the heatmap are the copy numbers amplified or deleted in more than two sites within one patient. The copy number for each site is also provided. Indicated genes under each heatmap are copy numbers only amplified in brain metastasis. Magnetic resonance images are shown on the right side of each heatmap. There is no image for the primary tumor of patient C as the patient had an unplanned excision of the primary tumor. (B) Mutated genes and the types of alterations in the order of cancer progression for patients C and D. PLPS, pleomorphic liposarcoma; UPS, undifferentiated pleomorphic sarcoma.

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  Fig. 2. Gene expression comparison of soft tissue sarcoma with brain metastasis to The Cancer Genome Atlas sarcoma (TCGA-SARC) samples. (A) The left panel shows a volcano plot. Each dot represents each gene. The x-axis value represents fold change (mean gene expression of the study cohort divided by the TCGA-SARC cohort) and the y-axis value represents the p-value. The blue dashed line denotes a fold change value of 2 and the green dashed line denotes a p-value of 1.0×10–7. Red dots are the genes that are significantly upregulated in the study cohort. Gene ontology analysis was done with the genes of the red dots. The right panel shows the significantly enriched gene ontology terms with p-values. (B) Enrichment plot of the two pathways that were significantly enriched in the study cohort by Gene Set Enrichment Analysis analysis. (C) Normalized enrichment scores of the four pathways. KEGG, Kyoto Encyclopedia of Genes and Genomes.

Reference

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