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Genetic Heterogeneity of Esophageal Squamous Cell Carcinoma with Inherited Family History
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor with significant geographical variation and familial aggregation. However, the potentially different mechanisms underlying tumorigenesis in patients with ESCC with and without a family history of the disease remain unc...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481280/ https://www.ncbi.nlm.nih.gov/pubmed/32943884 http://dx.doi.org/10.2147/OTT.S262512 |
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author | He, Wenwu Leng, Xuefeng Yang, Yanyu Peng, Lin Shao, Yang Li, Xue Han, Yongtao |
author_facet | He, Wenwu Leng, Xuefeng Yang, Yanyu Peng, Lin Shao, Yang Li, Xue Han, Yongtao |
author_sort | He, Wenwu |
collection | PubMed |
description | BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor with significant geographical variation and familial aggregation. However, the potentially different mechanisms underlying tumorigenesis in patients with ESCC with and without a family history of the disease remain unclear. In this study, the genes mutated in familial and nonfamilial ESCC were analyzed. Further, we aimed to explore the genes related to ESCC and attempt to identify potential patients in families with a history of ESCC. METHODS: Next-generation sequencing technology was used to examine germline mutations and mutation profiles in 36 matched tumor-normal ESCC specimens. Additionally, tumor mutational burden (TMB) values were measured in two cohorts. RESULTS: We identified four novel germline mutations in patients with familial ESCC, in BAX (c.121dupG: p.E41G), CDKN2A (c.374dupA: p.D125E), TP53 (c.856G>A: p.E286K), and CHEK1 (c.923+1G>A). Mutation profiles revealed that patients with and without a family history of ESCC had similar high-frequency gene mutation profiles, among which TP53 was the most commonly mutated gene. Additionally, tumor-specific mutated genes in patients with a positive family history of ESCC were APC, AKT3, DPYD, EP300, NFE2L2, PPP2R1A, RUNX1, and VEGFA, while those in patients without a family history of ESCC were CXCR4, PIK3R2, SMARCA4, and TTF1. Moreover, patients with positive family history had significantly higher TMB values (7.8 ± 4.1 vs 5.0 ± 2.4, for patients with and without a family history, respectively; P = 0.038). CONCLUSION: Our results identified mutation profiles in patients with familial and nonfamilial ESCC, and identified germline mutations in patients with positive history. TMB values may be informative for immunotherapy approaches in familial ESCC. |
format | Online Article Text |
id | pubmed-7481280 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-74812802020-09-16 Genetic Heterogeneity of Esophageal Squamous Cell Carcinoma with Inherited Family History He, Wenwu Leng, Xuefeng Yang, Yanyu Peng, Lin Shao, Yang Li, Xue Han, Yongtao Onco Targets Ther Original Research BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor with significant geographical variation and familial aggregation. However, the potentially different mechanisms underlying tumorigenesis in patients with ESCC with and without a family history of the disease remain unclear. In this study, the genes mutated in familial and nonfamilial ESCC were analyzed. Further, we aimed to explore the genes related to ESCC and attempt to identify potential patients in families with a history of ESCC. METHODS: Next-generation sequencing technology was used to examine germline mutations and mutation profiles in 36 matched tumor-normal ESCC specimens. Additionally, tumor mutational burden (TMB) values were measured in two cohorts. RESULTS: We identified four novel germline mutations in patients with familial ESCC, in BAX (c.121dupG: p.E41G), CDKN2A (c.374dupA: p.D125E), TP53 (c.856G>A: p.E286K), and CHEK1 (c.923+1G>A). Mutation profiles revealed that patients with and without a family history of ESCC had similar high-frequency gene mutation profiles, among which TP53 was the most commonly mutated gene. Additionally, tumor-specific mutated genes in patients with a positive family history of ESCC were APC, AKT3, DPYD, EP300, NFE2L2, PPP2R1A, RUNX1, and VEGFA, while those in patients without a family history of ESCC were CXCR4, PIK3R2, SMARCA4, and TTF1. Moreover, patients with positive family history had significantly higher TMB values (7.8 ± 4.1 vs 5.0 ± 2.4, for patients with and without a family history, respectively; P = 0.038). CONCLUSION: Our results identified mutation profiles in patients with familial and nonfamilial ESCC, and identified germline mutations in patients with positive history. TMB values may be informative for immunotherapy approaches in familial ESCC. Dove 2020-09-03 /pmc/articles/PMC7481280/ /pubmed/32943884 http://dx.doi.org/10.2147/OTT.S262512 Text en © 2020 He et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research He, Wenwu Leng, Xuefeng Yang, Yanyu Peng, Lin Shao, Yang Li, Xue Han, Yongtao Genetic Heterogeneity of Esophageal Squamous Cell Carcinoma with Inherited Family History |
title | Genetic Heterogeneity of Esophageal Squamous Cell Carcinoma with Inherited Family History |
title_full | Genetic Heterogeneity of Esophageal Squamous Cell Carcinoma with Inherited Family History |
title_fullStr | Genetic Heterogeneity of Esophageal Squamous Cell Carcinoma with Inherited Family History |
title_full_unstemmed | Genetic Heterogeneity of Esophageal Squamous Cell Carcinoma with Inherited Family History |
title_short | Genetic Heterogeneity of Esophageal Squamous Cell Carcinoma with Inherited Family History |
title_sort | genetic heterogeneity of esophageal squamous cell carcinoma with inherited family history |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481280/ https://www.ncbi.nlm.nih.gov/pubmed/32943884 http://dx.doi.org/10.2147/OTT.S262512 |
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