scholarly journals Peer Review #1 of "Whole genome sequencing analysis identifies recurrent structural alterations in esophageal squamous cell carcinoma (v0.2)"

2020 ◽  
Author(s):  
M Ahmed
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Whole Genome Sequencing ◽  
Peer Review ◽  
Genome Sequencing ◽  
Squamous Cell ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Structural Alterations

scholarly journals Whole genome sequencing analysis identifies recurrent structural alterations in esophageal squamous cell carcinoma

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9294 ◽  
Author(s):  
Munmee Dutta ◽  
Hidewaki Nakagawa ◽  
Hiroaki Kato ◽  
Kazuhiro Maejima ◽  
Shota Sasagawa ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Squamous Cell ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Structural Alterations ◽  
Mutational Landscape

Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer in the Asian region, including Japan. A previous study reported mutational landscape of Japanese ESCCs by using exome sequencing. However, somatic structural alterations were yet to be explored. To provide a comprehensive mutational landscape, we performed whole genome sequencing (WGS) analysis of biopsy specimens from 20 ESCC patients in a Japanese population. WGS analysis identified non-silent coding mutations of TP53, ZNF750 and FAT1 in ESCC. We detected six mutational signatures in ESCC, one of which showed significant association with smoking status. Recurrent structural variations, many of which were chromosomal deletions, affected genes such as LRP1B, TTC28, CSMD1, PDE4D, SDK1 and WWOX in 25%–30% of tumors. Somatic copy number amplifications at 11q13.3 (CCND1), 3q26.33 (TP63/SOX2), and 8p11.23 (FGFR1) and deletions at 9p21.3 (CDKN2A) were identified. Overall, these multi-dimensional view of genomic alterations improve the understanding of the ESCC development at molecular level and provides future prognosis and therapeutic implications for ESCC in Japan.

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.

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
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