| Title |
Genomic alterations of plasma cell-free DNAs in small cell lung cancer and their clinical relevance
|
|---|---|
| Published in |
Lung Cancer (01695002), April 2018
|
| DOI | 10.1016/j.lungcan.2018.04.008 |
| Pubmed ID | |
| Authors |
Meijun Du, Jonathan Thompson, Hannah Fisher, Peng Zhang, Chiang-Ching Huang, Liang Wang |
| Abstract |
To identify genomic variations in cell-free DNA (cfDNA) and evaluate their clinical utility in small cell lung cancer (SCLC). We performed whole genome sequencing using plasma cfDNAs derived from 24 SCLC patients for copy number variation (CNV) analysis, and targeted sequencing using 17 pairs of plasma cfDNA and their matched gDNA for mutation analysis. We defined somatic mutations by comparing cfDNA to its matched gDNA with 5% variant alleles as the cutoff for mutation calls. We applied Kaplan-Meier to correlate the genomic alterations with overall survival (OS) and progression-free survival (PFS). We observed widespread somatic copy-number alterations and mutations, including amplification of MYC at 8q24, FGF10 at 5p13, SOX2 at 3q26 and FGFR1 at 8p12, as well as deletion of TP53 at 17p13, RASSF1 at 3p21.3, RB1 at 13q14.2, FHIT at 3p14, and PTEN at 10q23. The most frequent mutations were genes involved in chromatin regulation (KMT2D, ARID1A, SETBP1 and PBRM1), PI3K/MTOR pathway(MTOR,PIK13G), Notch1 signalling pathway (NOTCH1), and DNA repair related gene ATRX. Kaplan-Meier analysis revealed poor OS and PFS in patients with somatic mutations in gene SETBP1 (P = 0.0061/0.0264, HR = 4.785/3.841, 95% CI = 2.014-28.25/1.286-16.58) and PBRM1 (P = 0.0276/0.0286, HR = 3.532/3.506, 95% CI = 1.275 to 25.34/1.26-24.87). Poor OS was also associated with somatic mutations in ATRX (P = 0.0099, HR = 4.024, 95% CI = 1.926-42.95), EP300 (P = 0.025/0.0622, HR = 3.382/2.891, 95% CI = 1.448-27.76/1.013-17.29), while poor PFS was associated with ATM mutation (P = 0.0038, HR = 4.604, 95% CI = 2.211-40.93). The mutation index produced by summing up the number of mutations in the five genes was significantly associated with the poor OS/PFS (P = 0.0185/0.0294) after adjusting the effect of the stage. Our result supports blood plasma as a promising sample source for the genomic analysis in SCLC patients whose tumor tissues are scarcely available and demonstrates potential clinical utilities of cfDNA-based liquid biopsy for clinical management of this deadly disease. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 49 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 9 | 18% |
| Student > Master | 6 | 12% |
| Researcher | 4 | 8% |
| Student > Doctoral Student | 2 | 4% |
| Other | 2 | 4% |
| Other | 7 | 14% |
| Unknown | 19 | 39% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 10 | 20% |
| Medicine and Dentistry | 9 | 18% |
| Agricultural and Biological Sciences | 4 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 4% |
| Unspecified | 2 | 4% |
| Other | 3 | 6% |
| Unknown | 19 | 39% |
Attention Score in Context
This research output has an Altmetric Attention Score of 10. 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 23 May 2019.
All research outputs
#3,623,572
of 25,382,440 outputs
Outputs from Lung Cancer (01695002)
#420
of 3,036 outputs
Outputs of similar age
#70,846
of 343,384 outputs
Outputs of similar age from Lung Cancer (01695002)
#6
of 43 outputs
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