Genome-wide screening for genetic alterations in esophageal cancer by aCGH identifies 11q13 amplification oncogenes associated with nodal metastasis.

<h4>Background</h4>Esophageal squamous cell carcinoma (ESCC) is highly prevalent in China and other Asian countries, as a major cause of cancer-related mortality. ESCC displays complex chromosomal abnormalities, including multiple structural and numerical aberrations. Chromosomal abnorma...

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Autores principales: Jianming Ying, Ling Shan, Jisheng Li, Lan Zhong, Liyan Xue, Hong Zhao, Lili Li, Cordelia Langford, Lei Guo, Tian Qiu, Ning Lu, Qian Tao
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spelling oai:doaj.org-article:683641f2008b433db638f3513c283fed2021-11-18T07:14:24ZGenome-wide screening for genetic alterations in esophageal cancer by aCGH identifies 11q13 amplification oncogenes associated with nodal metastasis.1932-620310.1371/journal.pone.0039797https://doaj.org/article/683641f2008b433db638f3513c283fed2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22761904/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Esophageal squamous cell carcinoma (ESCC) is highly prevalent in China and other Asian countries, as a major cause of cancer-related mortality. ESCC displays complex chromosomal abnormalities, including multiple structural and numerical aberrations. Chromosomal abnormalities, such as recurrent amplifications and homozygous deletions, directly contribute to tumorigenesis through altering the expression of key oncogenes and tumor suppressor genes.<h4>Methodology/principle findings</h4>To understand the role of genetic alterations in ESCC pathogenesis and identify critical amplification/deletion targets, we performed genome-wide 1-Mb array comparative genomic hybridization (aCGH) analysis for 10 commonly used ESCC cell lines. Recurrent chromosomal gains were frequently detected on 3q26-27, 5p15-14, 8p12, 8p22-24, 11q13, 13q21-31, 18p11 and 20q11-13, with frequent losses also found on 8p23-22, 11q22, 14q32 and 18q11-23. Gain of 11q13.3-13.4 was the most frequent alteration in ESCC. Within this region, CCND1 oncogene was identified with high level of amplification and overexpression in ESCC, while FGF19 and SHANK2 was also remarkably over-expressed. Moreover, a high concordance (91.5%) of gene amplification and protein overexpression of CCND1 was observed in primary ESCC tumors. CCND1 amplification/overexpression was also significantly correlated with the lymph node metastasis of ESCC.<h4>Conclusion</h4>These findings suggest that genomic gain of 11q13 is the major mechanism contributing to the amplification. Novel oncogenes identified within the 11q13 amplicon including FGF19 and SHANK2 may play important roles in ESCC tumorigenesis.Jianming YingLing ShanJisheng LiLan ZhongLiyan XueHong ZhaoLili LiCordelia LangfordLei GuoTian QiuNing LuQian TaoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39797 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jianming Ying
Ling Shan
Jisheng Li
Lan Zhong
Liyan Xue
Hong Zhao
Lili Li
Cordelia Langford
Lei Guo
Tian Qiu
Ning Lu
Qian Tao
Genome-wide screening for genetic alterations in esophageal cancer by aCGH identifies 11q13 amplification oncogenes associated with nodal metastasis.
description <h4>Background</h4>Esophageal squamous cell carcinoma (ESCC) is highly prevalent in China and other Asian countries, as a major cause of cancer-related mortality. ESCC displays complex chromosomal abnormalities, including multiple structural and numerical aberrations. Chromosomal abnormalities, such as recurrent amplifications and homozygous deletions, directly contribute to tumorigenesis through altering the expression of key oncogenes and tumor suppressor genes.<h4>Methodology/principle findings</h4>To understand the role of genetic alterations in ESCC pathogenesis and identify critical amplification/deletion targets, we performed genome-wide 1-Mb array comparative genomic hybridization (aCGH) analysis for 10 commonly used ESCC cell lines. Recurrent chromosomal gains were frequently detected on 3q26-27, 5p15-14, 8p12, 8p22-24, 11q13, 13q21-31, 18p11 and 20q11-13, with frequent losses also found on 8p23-22, 11q22, 14q32 and 18q11-23. Gain of 11q13.3-13.4 was the most frequent alteration in ESCC. Within this region, CCND1 oncogene was identified with high level of amplification and overexpression in ESCC, while FGF19 and SHANK2 was also remarkably over-expressed. Moreover, a high concordance (91.5%) of gene amplification and protein overexpression of CCND1 was observed in primary ESCC tumors. CCND1 amplification/overexpression was also significantly correlated with the lymph node metastasis of ESCC.<h4>Conclusion</h4>These findings suggest that genomic gain of 11q13 is the major mechanism contributing to the amplification. Novel oncogenes identified within the 11q13 amplicon including FGF19 and SHANK2 may play important roles in ESCC tumorigenesis.
format article
author Jianming Ying
Ling Shan
Jisheng Li
Lan Zhong
Liyan Xue
Hong Zhao
Lili Li
Cordelia Langford
Lei Guo
Tian Qiu
Ning Lu
Qian Tao
author_facet Jianming Ying
Ling Shan
Jisheng Li
Lan Zhong
Liyan Xue
Hong Zhao
Lili Li
Cordelia Langford
Lei Guo
Tian Qiu
Ning Lu
Qian Tao
author_sort Jianming Ying
title Genome-wide screening for genetic alterations in esophageal cancer by aCGH identifies 11q13 amplification oncogenes associated with nodal metastasis.
title_short Genome-wide screening for genetic alterations in esophageal cancer by aCGH identifies 11q13 amplification oncogenes associated with nodal metastasis.
title_full Genome-wide screening for genetic alterations in esophageal cancer by aCGH identifies 11q13 amplification oncogenes associated with nodal metastasis.
title_fullStr Genome-wide screening for genetic alterations in esophageal cancer by aCGH identifies 11q13 amplification oncogenes associated with nodal metastasis.
title_full_unstemmed Genome-wide screening for genetic alterations in esophageal cancer by aCGH identifies 11q13 amplification oncogenes associated with nodal metastasis.
title_sort genome-wide screening for genetic alterations in esophageal cancer by acgh identifies 11q13 amplification oncogenes associated with nodal metastasis.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/683641f2008b433db638f3513c283fed
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