Dataset Information

Mutational Landscape of Esophageal Squamous Cell Carcinoma in an Indian Cohort.

ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is the most common histological subtype of esophageal cancer in India. Cigarette smoking and chewing tobacco are known risk factors associated with ESCC. However, genomic alterations associated with ESCC in India are not well-characterized. In this study, we carried out exome sequencing to characterize the mutational landscape of ESCC tumors from subjects with a varied history of tobacco usage. Whole exome sequence analysis of ESCC from an Indian cohort revealed several genes that were mutated or had copy number changes. ESCC from tobacco chewers had a higher frequency of C:G > A:T transversions and 2-fold enrichment for mutation signature 4 compared to smokers and non-users of tobacco. Genes, such as TP53, CSMD3, SYNE1, PIK3CA, and NOTCH1 were found to be frequently mutated in Indian cohort. Mutually exclusive mutation patterns were observed in PIK3CA-NOTCH1, DNAH5-ZFHX4, MUC16-FAT1, and ZFHX4-NOTCH1 gene pairs. Recurrent amplifications were observed in 3q22-3q29, 11q13.3-q13.4, 7q22.1-q31.1, and 8q24 regions. Approximately 53% of tumors had genomic alterations in PIK3CA making this pathway a promising candidate for targeted therapy. In conclusion, we observe enrichment of mutation signature 4 in ESCC tumors from patients with a history of tobacco chewing. This is likely due to direct exposure of esophagus to tobacco carcinogens when it is chewed and swallowed. Genomic alterations were frequently observed in PIK3CA-AKT pathway members independent of the history of tobacco usage. PIK3CA pathway can be potentially targeted in ESCC which currently has no effective targeted therapeutic options.

SUBMITTER: Mangalaparthi KK

PROVIDER: S-EPMC7469928 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mutational Landscape of Esophageal Squamous Cell Carcinoma in an Indian Cohort.

Mangalaparthi Kiran K KK Patel Krishna K Khan Aafaque A AA Manoharan Malini M Karunakaran Coral C Murugan Sakthivel S Gupta Ravi R Gupta Rohit R Khanna-Gupta Arati A Chaudhuri Amitabha A Kumar Prashant P Nair Bipin B Kumar Rekha V RV Prasad T S Keshava TSK Chatterjee Aditi A Pandey Akhilesh A Gowda Harsha H

Frontiers in oncology 20200820

Esophageal squamous cell carcinoma (ESCC) is the most common histological subtype of esophageal cancer in India. Cigarette smoking and chewing tobacco are known risk factors associated with ESCC. However, genomic alterations associated with ESCC in India are not well-characterized. In this study, we carried out exome sequencing to characterize the mutational landscape of ESCC tumors from subjects with a varied history of tobacco usage. Whole exome sequence analysis of ESCC from an Indian cohort ...[more]

PMID: 32974170

Similar Datasets

Project description:BackgroundImmunotherapy has achieved remarkable efficacy in treating oesophageal squamous cell carcinoma (ESCC). However, this treatment has limited efficacy in some patients. An increasing number of evidence suggested that immune cells within the tumour microenvironment (TME) are strongly related to immunotherapy response and patient prognosis. Thus, the landscape of immune cell infiltration (ICI) in ESCC needs to be mapped.MethodsIn the study, the ICI pattern in 206 cases of ESCC was characterised by two algorithms, namely, CIBERSORT and single-sample gene set enrichment analysis (ssGSEA). The ICI score of each specimen was calculated by principal component analysis (PCA) according to ICI signature genes A (ICISGA) and B (ICISGB). The prognostic difference was evaluated by using the Kaplan-Meier method. The related pathways of ICI score were investigated by applying gene set enrichment analysis (GSEA). The R packages of 'regplot', 'timeROC' and 'rms' were applied for the construction of nomogram model.ResultThree TME subtypes were identified with no prognostic implication. A total of 333 differentially expressed genes (DEGs) among immune subtypes were determined, among which ICISGA and ICISGB were identified. Finally, ICI scores were constructed, and the patients were grouped into high or low ICI score group. Compared with the low ICI score group, the high ICI score group had better prognosis. GSEA revealed that the high ICI score group referred to multiple signalling pathways, including B cell receptor, Fc gamma R-mediated phagocytosis, NOD-like receptor and TGF-β signalling pathways. In addition, the nomogram model was constructed to evaluate 1-, 3- and 5-year probability of death in an ESCC patient. The ROC and calibration curves indicated that the model has a good discrimination ability.ConclusionWe depicted a comprehensive ICI landscape in ESCC. ICI score may be used as a predictor of survival rate, which may be helpful for guiding immunotherapy in the future.

Dataset Information

Mutational Landscape of Esophageal Squamous Cell Carcinoma in an Indian Cohort.

Publications

Mutational Landscape of Esophageal Squamous Cell Carcinoma in an Indian Cohort.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets