Genome-Wide Copy Number Variation of Circulating Cell-Free DNA As a Biomarker in Head and Neck Cancer Patients Treated With Immunotherapy

2021 ◽  
Author(s):  
Yunshu Zhu ◽  
Sheng Yang ◽  
Liping Jiang ◽  
Xiaobing Wang ◽  
Xiaohui He
Keyword(s):  
Head And Neck Cancer ◽  
Copy Number Variation ◽  
Head And Neck ◽  
Cancer Patients ◽  
Neck Cancer ◽  
Copy Number ◽  
Cell Free Dna ◽  
Free Dna ◽  
Genome Wide ◽  
Number Variation

The mutational landscape of circulating cell-free DNA to identify neoadjuvant chemotherapy response in colorectal cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15096-e15096
Author(s):  
Yanlong Liu ◽  
Xiaoli Wei ◽  
Xinying Shi ◽  
Ying Yang ◽  
Lili Fu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Copy Number Variation ◽  
Cancer Patients ◽  
Candidate Genes ◽  
Copy Number ◽  
Free Dna ◽  
Number Variation ◽  
Colorectal Cancer Patients ◽  
Response To Neoadjuvant Chemotherapy

e15096 Background: The neoadjuvant chemotherapy plays an important role in the current treatment of colorectal cancer (CRC), even though parts of patients could not be benefit from it. This study was aimed to explore the specific mutational profile of plasma cell free DNA (cfDNA) in CRC patients with or without response to neoadjuvant chemotherapy. Methods: 16 eligible CRC patients were enrolled in this study from Harbin Medical University Cancer Hospital. These patients were divided into two groups: with response ( R, n = 8) and without response (NR, n = 8) to neoadjuvant chemotherapy. All patients received neoadjuvant chemotherapy and their baseline blood samples were collected. The cfDNA fragments were extracted for enrichment of a panel covering exon regions of 1,086 genes. Gene alterations were analyzed to investigate the relationship between genetic characterizations of cfDNA and response to neoadjuvant chemotherapy. Results: Principal component (PCA) analysis for copy number variation(CNV) of cfDNA differed significantly in two groups. In the R group, there were higher frequency CNV loss in ABL-1, ERBB3, SMO, IGF1R, AURKA, PDGFRA, IDH1, BRAF, PIK3CB, NRAS, NF1, MITF, PTCH1 genes, and CNV gain in MTRR, HSP90AA1, VHL, CREBBP, CHEK2, DDR2, MUTYH, NCOA1, XPC, FANCA genes. Regarding to the area under the ROC curve, CNV of these genes had a high value of 0.967, which implied that CNV of the candidate genes have predictive value for identifying response to neoadjuvant chemotherapy in CRC patients. Furthermore, the Copy Number Instability (CNI) value of R group was significantly higher than NR group(p = 0.0014). Conclusions: The candidate genes’ copy number variation and CNI value of baseline plasma cfDNA can identify the colorectal cancer patients with response or without response to neoadjuvant chemotherapy in this small cohort. The molecular profile of cfDNA in plasma may be a potential biomarker for predicting the response to neoadjuvant chemotherapy in colorectal cancer patients. These findings warrant further expanded prospective cohorts to validate.

Copy number variation of genes in cell-free DNA in patients with lung adenocarcinoma.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e24060-e24060
Author(s):  
Denis S. Kutilin ◽  
Igor N. Turkin ◽  
Dmitry I. Vodolazhsky ◽  
Tamara G. Ayrapetova ◽  
Sergey P. Pyltsin ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Lung Adenocarcinoma ◽  
Copy Number ◽  
Cell Free Dna ◽  
Free Dna ◽  
Number Variation

Comparison of circulating tumor cells and cell-free DNA in the molecular characterization of patients with head and neck cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18521-e18521
Author(s):  
Santiago Cabezas-Camarero ◽  
Vanesa García-Barberán ◽  
Virginia De la Orden-García ◽  
Beatriz Mediero-Valeros ◽  
Isabel Díaz-Millán ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Parotid Gland ◽  
Head And Neck ◽  
Molecular Characterization ◽  
Neck Cancer ◽  
Liquid Biopsy ◽  
Digital Pcr ◽  
Cell Free Dna ◽  
Free Dna

e18521 Background: The role of liquid biopsy in diagnosis and therapy monitoring in patients with head and neck cancer has been much less studied compared to other cancers. Our aim was to evaluate the perfomance in the isolation and recovery for molecular characterization of circulating tumour cells (CTC) of a new immunoafinity-based method and to compare it with the molecular diagnostic yield of plasma cell-free DNA. Methods: Patients with recurrent/metastatic (RM) head and neck cancer (HNC) were enrolled prospectively. Forty mililiters (ml) of plasma were collected at one or several time-points. First blood draw was always collected before starting a new therapeutic intervention or at the time of radiologic progression. For CTC detection and isolation, either anti-EpCAM or both anti-EpCAM + anti-EGFR antibodies were used. Digital PCR and castPCR were used to study KRAS and PI3KCA mutations in non-squamous HNC. A 15-gene customized NGS panel was used to characterized both CTC and cfDNA in patients with squamous HNC. Results: Between February 2016 and October 2018, 14 patients with R/M HNC were included (n = 1 local-only disease, n = 10 local and distant disease, n = 3 distant-only disease). Squamous histology (S): n = 9. Non-squamous (NS): n = 5 (1 naso-ethmoidal intestinal-type adenocarcinoma, 1 parotid gland exadenoma pleomorfic carcinoma, 2 parotid-gland salivary duct carcinomas (SDC), 1 parotid-gland high-grade neuroendocrine carcinoma). Twenty-five CTC determinations were performed. In 5 patients serial CTC determinations were performed. Median CTC was 4 (min-max: 0-49). Median CTC among 11 CTC determinations in S-HNC was 4 (min-max: 0-49). Median CTC was 3 CTC (min-max: 0-26) among the 14 determinations performed in NS-HNC. Digital PCR unveiled mutations in CTC and in cfDNA in 2 of 4 patients tested with NS histology (KRAS, PIK3CA), with one of them being concordant for the specific mutation. NGS unveiled mutations in CTC in 7/9 patients and in cfDNA in 6/9 patients, with only one loci-concordant case between CTC and plasma. Conclusions: IsoFlux detected CTC in the majority of patients with R/M HNC, regardless of the histologic type, and allowed for molecular characterization of CTC using different techniques for mutational analysis. Both NGS and digital PCR allowed for the detection in cell-free DNA of commonly mutated genes in HNC. Liquid biopsy should be more actively studied in this disease in order to better define its role in diagnosis and therapeutic monitoring.

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