The Presence of Genomic Instability in Cerebrospinal Fluid in Patients with Meningeal Metastasis

Figures & data

Table 1 Basic Characteristics of Meningeal Metastasis Patients

Indices
Age (y)	53.53±10.51
Sex (male, %)	6 (40)
Diagnosis
Lung adenocarcinoma	10 (66.6%)
Breast cancer	3 (20%)
Gastric cancer	1 (6.7%)
Colorectal cancer	1 (6.7%)
Genomic instability
Yes	12 (80%)
No	3 (20%)
TMB in plasma	4.174±5.4
TMB in CSF	5.498±3.55
Treatment
Targeted therapy	12 (80%)
CSF chemotherapy	7 (46.7%)
Overall survival (month)	36.53±27.46
DS-GPA	1.7±0.676
Outcome (survived, %)	5 (33.33)

Abbreviations: TMB, tumor mutation burden; CSF, cerebrospinal fluid; DS-GPA, diagnosis-specific graded prognostic.

Figure 1 The blood and cerebrospinal fluid of 15 meningeal metastasis patients and 1 brain parenchymal metastasis patient were detected by a panel of 543 cancer-related genes. Heatmap displayed gene mutations in CSF and blood of these patients.

Figure 2 (A–L) A panel analysis of 543 cancer-related genes in blood and CSF in 12 patients with genomic instability. (M–O) A panel analysis of 543 cancer-related genes in blood and CSF in three patients with genomic stability. (P) A panel analysis of 543 cancer-related genes in blood and CSF in a brain parenchymal metastasis patient.

Abbreviations:BC, white blood cells; CF, plasma; CSF, cerebrospinal fluid; CSFCD, cerebrospinal fluid precipitation; FFPE, formalin-fixed, paraffin-embedded tissues.

Table 2 Genomic Variation in Cerebrospinal Fluid of the 15 Meningeal Metastasis Patients

Genomic Variation	Genomic Instability (n)	Genomic Stability (n)	Exon	Frequency (%)/Gene Copy Number (n) in CSF-SQ
ERBB2 p. V659E	1	–	17	26.8%
Increased copy number of ERBB2	1	–	–	n=35.03
EGFR p. T790M	1	–	19	25.82%
EGFR p. L858R	1	–	21	42.62%
EGFR p. G719A	–	1	18	3.55%
EGFR exon 20 insertion			20
EGFR p. A767_V769dupASV	1	–		37.17%
ERBB2 p.Y772_A775dupYVMA	1	–		72.41%
EGFR exon 19 deletion			19
EGFR p.E746_A750delELREA	3	–		26.09%
				80.65%
				9.81%
Increased copy number of MET	2	–	–	n=2.65
				n=3.1
KRAS p. G13R	1	–	2	19.32%
ALK p. L1196M	1	–	23	13.87%

Notes: N referred number of cases. Autosomal gene copy number n=2; n<1.5 mean reduced copy number; n> 2.5 mean increased copy number. (–): no data.

Abbreviation: CSF-SQ, cerebrospinal fluid supernatant.

Figure 3 (A–F) Copy number variation in blood and CSF in six meningeal metastasis patients with genomic instability. The log2 ratio value is plotted on the y-axis; the x-axis represents chromosomes. Red indicates copy number gain, green indicates copy number loss, and blue indicates no change.

Abbreviations: CF, plasma; CSF-SQ, cerebrospinal fluid supernatant.

Figure 4 (A and B) Copy number variation in blood and CSF in two meningeal metastasis patients with genomic stability. (C) Copy number variation in blood and CSF in brain parenchymal metastasis case with genomic stability. The log2 ratio value is plotted on the y-axis; the x-axis represents chromosomes. Red indicates copy number gain, green indicates copy number loss, and blue indicates no change.

Abbreviations: CF, plasma; CSF-SQ, cerebrospinal fluid supernatant.

Table 3 Aneuploidy Score of Patients with Genomic Instability or Genomic Stability

Patient No.	Aneuploidy Score of Genomic Instability		Aneuploidy Score of Genomic Stability
	CSF-SQ	CF	CSF-SQ	CF
2	15	0	–	–
3	–	–	0	0
4	28	0	–	–
5	23	22	–	–
6	28	29	–	–
7	–	–	0	0
8	26	14	–	–
9	25	0	–	–
16	–	–	2	0

Abbreviations: CSF-SQ, cerebrospinal fluid supernatant; CF, plasma.

Figure 5 Overall survival analysis between meningeal metastasis patients with genomic instability and genomic stability.