Cargando…

Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance

Oesophageal carcinoma is the fourth leading cause of cancer-related death in China, and more than 90% of these tumours are oesophageal squamous cell carcinoma (ESCC). Although several ESCC genomic sequencing studies have identified mutated somatic genes, the number of samples in each study was relat...

Descripción completa

Detalles Bibliográficos
Autores principales: Du, Peina, Huang, Peide, Huang, Xuanlin, Li, Xiangchun, Feng, Zhimin, Li, Fengyu, Liang, Shaoguang, Song, Yongmei, Stenvang, Jan, Brünner, Nils, Yang, Huanming, Ou, Yunwei, Gao, Qiang, Li, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681595/
https://www.ncbi.nlm.nih.gov/pubmed/29127303
http://dx.doi.org/10.1038/s41598-017-14909-5
_version_ 1783277936838705152
author Du, Peina
Huang, Peide
Huang, Xuanlin
Li, Xiangchun
Feng, Zhimin
Li, Fengyu
Liang, Shaoguang
Song, Yongmei
Stenvang, Jan
Brünner, Nils
Yang, Huanming
Ou, Yunwei
Gao, Qiang
Li, Lin
author_facet Du, Peina
Huang, Peide
Huang, Xuanlin
Li, Xiangchun
Feng, Zhimin
Li, Fengyu
Liang, Shaoguang
Song, Yongmei
Stenvang, Jan
Brünner, Nils
Yang, Huanming
Ou, Yunwei
Gao, Qiang
Li, Lin
author_sort Du, Peina
collection PubMed
description Oesophageal carcinoma is the fourth leading cause of cancer-related death in China, and more than 90% of these tumours are oesophageal squamous cell carcinoma (ESCC). Although several ESCC genomic sequencing studies have identified mutated somatic genes, the number of samples in each study was relatively small, and the molecular basis of ESCC has not been fully elucidated. Here, we performed an integrated analysis of 490 tumours by combining the genomic data from 7 previous ESCC projects. We identified 18 significantly mutated genes (SMGs). PTEN, DCDC1 and CUL3 were first reported as SMGs in ESCC. Notably, the AJUBA mutations and mutational signature4 were significantly correlated with a poorer survival in patients with ESCC. Hierarchical clustering analysis of the copy number alteration (CNA) of cancer gene census (CGC) genes in ESCC patients revealed three subtypes, and subtype3 exhibited more CNAs and marked for worse prognosis compared with subtype2. Moreover, database annotation suggested that two significantly differential CNA genes (PIK3CA and FBXW7) between subtype3 and subtype2 may serve as therapeutic drug targets. This study has extended our knowledge of the genetic basis of ESCC and shed some light into the clinical relevance, which would help improve the therapy and prognosis of ESCC patients.
format Online
Article
Text
id pubmed-5681595
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-56815952017-11-17 Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance Du, Peina Huang, Peide Huang, Xuanlin Li, Xiangchun Feng, Zhimin Li, Fengyu Liang, Shaoguang Song, Yongmei Stenvang, Jan Brünner, Nils Yang, Huanming Ou, Yunwei Gao, Qiang Li, Lin Sci Rep Article Oesophageal carcinoma is the fourth leading cause of cancer-related death in China, and more than 90% of these tumours are oesophageal squamous cell carcinoma (ESCC). Although several ESCC genomic sequencing studies have identified mutated somatic genes, the number of samples in each study was relatively small, and the molecular basis of ESCC has not been fully elucidated. Here, we performed an integrated analysis of 490 tumours by combining the genomic data from 7 previous ESCC projects. We identified 18 significantly mutated genes (SMGs). PTEN, DCDC1 and CUL3 were first reported as SMGs in ESCC. Notably, the AJUBA mutations and mutational signature4 were significantly correlated with a poorer survival in patients with ESCC. Hierarchical clustering analysis of the copy number alteration (CNA) of cancer gene census (CGC) genes in ESCC patients revealed three subtypes, and subtype3 exhibited more CNAs and marked for worse prognosis compared with subtype2. Moreover, database annotation suggested that two significantly differential CNA genes (PIK3CA and FBXW7) between subtype3 and subtype2 may serve as therapeutic drug targets. This study has extended our knowledge of the genetic basis of ESCC and shed some light into the clinical relevance, which would help improve the therapy and prognosis of ESCC patients. Nature Publishing Group UK 2017-11-10 /pmc/articles/PMC5681595/ /pubmed/29127303 http://dx.doi.org/10.1038/s41598-017-14909-5 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Du, Peina
Huang, Peide
Huang, Xuanlin
Li, Xiangchun
Feng, Zhimin
Li, Fengyu
Liang, Shaoguang
Song, Yongmei
Stenvang, Jan
Brünner, Nils
Yang, Huanming
Ou, Yunwei
Gao, Qiang
Li, Lin
Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance
title Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance
title_full Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance
title_fullStr Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance
title_full_unstemmed Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance
title_short Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance
title_sort comprehensive genomic analysis of oesophageal squamous cell carcinoma reveals clinical relevance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681595/
https://www.ncbi.nlm.nih.gov/pubmed/29127303
http://dx.doi.org/10.1038/s41598-017-14909-5
work_keys_str_mv AT dupeina comprehensivegenomicanalysisofoesophagealsquamouscellcarcinomarevealsclinicalrelevance
AT huangpeide comprehensivegenomicanalysisofoesophagealsquamouscellcarcinomarevealsclinicalrelevance
AT huangxuanlin comprehensivegenomicanalysisofoesophagealsquamouscellcarcinomarevealsclinicalrelevance
AT lixiangchun comprehensivegenomicanalysisofoesophagealsquamouscellcarcinomarevealsclinicalrelevance
AT fengzhimin comprehensivegenomicanalysisofoesophagealsquamouscellcarcinomarevealsclinicalrelevance
AT lifengyu comprehensivegenomicanalysisofoesophagealsquamouscellcarcinomarevealsclinicalrelevance
AT liangshaoguang comprehensivegenomicanalysisofoesophagealsquamouscellcarcinomarevealsclinicalrelevance
AT songyongmei comprehensivegenomicanalysisofoesophagealsquamouscellcarcinomarevealsclinicalrelevance
AT stenvangjan comprehensivegenomicanalysisofoesophagealsquamouscellcarcinomarevealsclinicalrelevance
AT brunnernils comprehensivegenomicanalysisofoesophagealsquamouscellcarcinomarevealsclinicalrelevance
AT yanghuanming comprehensivegenomicanalysisofoesophagealsquamouscellcarcinomarevealsclinicalrelevance
AT ouyunwei comprehensivegenomicanalysisofoesophagealsquamouscellcarcinomarevealsclinicalrelevance
AT gaoqiang comprehensivegenomicanalysisofoesophagealsquamouscellcarcinomarevealsclinicalrelevance
AT lilin comprehensivegenomicanalysisofoesophagealsquamouscellcarcinomarevealsclinicalrelevance