scholarly journals Tumor Evolution and Intratumor Heterogeneity of an Oropharyngeal Squamous Cell Carcinoma Revealed by Whole-Genome Sequencing

Neoplasia ◽  
2013 ◽  
Vol 15 (12) ◽  
pp. 1371-IN7 ◽  
Author(s):  
Xinyi Cindy Zhang ◽  
Chang Xu ◽  
Ryan M. Mitchell ◽  
Bo Zhang ◽  
Derek Zhao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Squamous Cell ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Intratumor Heterogeneity ◽  
Tumor Evolution ◽  
Whole Genome

scholarly journals Low-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bella Nguyen ◽  
Nicholas C. Wong ◽  
Tim Semple ◽  
Michael Clark ◽  
Stephen Q. Wong ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Squamous Cell ◽  
Metastatic Cancer ◽  
Extracellular Vesicle ◽  
Whole Genome ◽  
Ffpe Samples ◽  
Low Coverage

AbstractLow-coverage whole-genome sequencing (LC-WGS) can provide insight into oncogenic molecular changes. Serum extracellular vesicles (EV) represent a novel liquid biopsy source of tumoral DNA. This study compared copy number alteration (CNA) profiles generated from LC-WGS of formalin-fixed paraffin-embedded (FFPE) tumoral DNA and EV-DNA obtained from cancer patients. Patients with squamous cell carcinoma of the base of tongue (n = 3) and cutaneous squamous cell carcinoma (n = 2) were included. LC-WGS (0.5-1X coverage) was performed on FFPE-DNA and serum EV-DNA. Similarity between CNA profiles was analysed using QDNAseq. FFPE samples had a mean CNA of 31 (range 17–50) over 1.9 × 109 (range 1.0–2.6 × 109) bp in length, and EV samples had a mean CNA value of 17 (range 7–19) over 7.6 × 108 (range 2.9–15 × 108) bp in length. A mean of 8 (range 0–21) CNA over 5.9 × 108 (range 1.6–14 × 108) bp in length was found to overlap between EV and FFPE-derived samples per patient. Although the mean correlation efficient between samples was r = 0.34 (range − .08 to 0.99), this was not statistically significant (p > 0.05). Regions of highest deletion and duplication in FFPE samples were not well reflected in the EV-DNA. Selected CNA regions in EV-associated DNA were reflective of the primary tumor, however appreciation of global CNA and areas of most significant change was lost. The utility of LC-WGS of EV-derived DNA is likely limited to molecular alterations of known interest.

scholarly journals Metabolic remodeling by TIGAR overexpression is a therapeutic target in esophageal squamous-cell carcinoma

2019 ◽  
Author(s):  
Jiahui Chu ◽  
Xiangjie Niu ◽  
Jiang Chang ◽  
Mingming Shao ◽  
Linna Peng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Squamous Cell ◽  
Chemotherapeutic Agents ◽  
Cytotoxic Agents ◽  
Whole Genome ◽  
Metabolic Remodeling

SummaryWhole-genome sequencing has identified many amplified genes in esophageal squamous-cell carcinoma (ESCC); however, their roles and the clinical relevance have yet elucidated. Here we show TP53-induced glycolysis and apoptosis regulator (TIGAR) is a major player in ESCC progression and chemoresistance. TIGAR reprograms glucose metabolism from glycolysis to the glutamine pathway through AMP-activated kinase, and its overexpression is correlated with poor disease outcomes. Tigar knockout mice have reduced ESCC growth and tumor burden. Treatment of TIGAR-overexpressed ESCC cell xenografts and patient-derived tumor xenografts in mice with combination of glutaminase inhibitor and chemotherapeutic agents achieves significant more efficacy than chemotherapy alone. These findings shed light on an important role of TIGAR in ESCC and provide evidence for targeted treatment of TIGAR-overexpressed ESCC.SignificanceEffective and target therapies are required for ESCC, one of the most common types of digestive OR cancer. Little has been known about the biology of ESCC progression or potential molecular targets OR for treatment. Whole-genome sequencing and RNA sequencing studies in ESCC have identified OR many recurrent copy number gain genes; however, the roles and druggable relevance of these OR genes remains poorly understood. Herein we demonstrate that TIGAR overexpression leads to OR metabolic remodeling, promoting ESCC progression and resistance to chemotherapeutic agents. OR Inhibiting the glutamine pathway significantly represses TIGAR-overexpressing ESCC growth and OR enhances tumor cell sensitization to cytotoxic agents. These findings might provide the rationale OR for clinical trials testing glutamine pathway inhibitors in combination with chemotherapy in OR TIGAR-expressing ESCC.

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