| Title |
Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid biopsy
|
|---|---|
| Published in |
Annals of Oncology, April 2018
|
| DOI | 10.1093/annonc/mdy009 |
| Pubmed ID | |
| Authors |
Y.S. Li, B.Y. Jiang, J.J. Yang, X.C. Zhang, Z. Zhang, J.Y. Ye, W.Z. Zhong, H.Y. Tu, H.J. Chen, Z. Wang, C.R. Xu, B.C. Wang, H.J. Du, S. Chuai, H. Han-Zhang, J. Su, Q. Zhou, X.N. Yang, W.B. Guo, H.H. Yan, Y.H. Liu, L.X. Yan, B. Huang, M.M. Zheng, Y.L. Wu |
| Abstract |
Leptomeningeal metastases (LM) are more frequent in non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM. Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled. 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26) and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared to those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; p < 0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% vs. 33.3%; p =0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression. CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Norway | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 89 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 89 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 18 | 20% |
| Student > Ph. D. Student | 10 | 11% |
| Other | 7 | 8% |
| Student > Master | 7 | 8% |
| Student > Bachelor | 5 | 6% |
| Other | 14 | 16% |
| Unknown | 28 | 31% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 21 | 24% |
| Biochemistry, Genetics and Molecular Biology | 19 | 21% |
| Agricultural and Biological Sciences | 6 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 4% |
| Nursing and Health Professions | 1 | 1% |
| Other | 4 | 4% |
| Unknown | 34 | 38% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 September 2018.
All research outputs
#16,725,651
of 25,382,440 outputs
Outputs from Annals of Oncology
#6,066
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Outputs of similar age
#210,933
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Outputs of similar age from Annals of Oncology
#100
of 147 outputs
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