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Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in gastric cancer

Gastric cancer (GC), one of the most common cancers worldwide, has a high mortality rate due to limited treatment options. Identifying novel and promising molecular targets is a major challenge that must be overcome if treatment of advanced GC is to be successful. Here, we used comparative genomic h...

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Autores principales: Kwon, Mi Jeong, Kim, Ryong Nam, Song, Kyoung, Jeon, Sinyoung, Jeong, Hae Min, Kim, Joo Seok, Han, Jinil, Hong, Sungyoul, Oh, Ensel, Choi, Jong-Sun, An, Jungsuk, Pollack, Jonathan R., Choi, Yoon-La, Park, Cheol-Keun, Shin, Young Kee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696175/
https://www.ncbi.nlm.nih.gov/pubmed/29190909
http://dx.doi.org/10.18632/oncotarget.21150
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author Kwon, Mi Jeong
Kim, Ryong Nam
Song, Kyoung
Jeon, Sinyoung
Jeong, Hae Min
Kim, Joo Seok
Han, Jinil
Hong, Sungyoul
Oh, Ensel
Choi, Jong-Sun
An, Jungsuk
Pollack, Jonathan R.
Choi, Yoon-La
Park, Cheol-Keun
Shin, Young Kee
author_facet Kwon, Mi Jeong
Kim, Ryong Nam
Song, Kyoung
Jeon, Sinyoung
Jeong, Hae Min
Kim, Joo Seok
Han, Jinil
Hong, Sungyoul
Oh, Ensel
Choi, Jong-Sun
An, Jungsuk
Pollack, Jonathan R.
Choi, Yoon-La
Park, Cheol-Keun
Shin, Young Kee
author_sort Kwon, Mi Jeong
collection PubMed
description Gastric cancer (GC), one of the most common cancers worldwide, has a high mortality rate due to limited treatment options. Identifying novel and promising molecular targets is a major challenge that must be overcome if treatment of advanced GC is to be successful. Here, we used comparative genomic hybridization and gene expression microarrays to examine genome-wide DNA copy number alterations (CNAs) and global gene expression in 38 GC samples from old and young patients. We identified frequent CNAs, which included copy number gains on chromosomes 3q, 7p, 8q, 20p, and 20q and copy number losses on chromosomes 19p and 21p. The most frequently gained region was 7p21.1 (55%), whereas the most frequently deleted region was 21p11.1 (50%). Recurrent highly amplified regions 17q12 and 7q31.1-7q31.31 harbored two well-known oncogenes: ERBB2 and MET. Correlation analysis of CNAs and gene expression levels identified CAPZA2 (co-amplified with MET) and genes GRB7, MIEN1, PGAP3, and STARD3 (co-amplified with ERBB2) as potential candidate cancer-promoting genes (CPGs). Public dataset analysis confirmed co-amplification of these genes with MET or ERBB2 in GC tissue samples, and revealed that high expression (except for PGAP3) was significantly associated with shorter overall survival. Knockdown of these genes using small interfering RNA led to significant suppression of GC cell proliferation and migration. Reduced GC cell proliferation mediated by CAPZA2 knockdown was attributable to attenuated cell cycle progression and increased apoptosis. This study identified novel candidate CPGs co-amplified with MET or ERBB2, and suggests that they play a functional role in GC.
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spelling pubmed-56961752017-11-29 Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in gastric cancer Kwon, Mi Jeong Kim, Ryong Nam Song, Kyoung Jeon, Sinyoung Jeong, Hae Min Kim, Joo Seok Han, Jinil Hong, Sungyoul Oh, Ensel Choi, Jong-Sun An, Jungsuk Pollack, Jonathan R. Choi, Yoon-La Park, Cheol-Keun Shin, Young Kee Oncotarget Research Paper Gastric cancer (GC), one of the most common cancers worldwide, has a high mortality rate due to limited treatment options. Identifying novel and promising molecular targets is a major challenge that must be overcome if treatment of advanced GC is to be successful. Here, we used comparative genomic hybridization and gene expression microarrays to examine genome-wide DNA copy number alterations (CNAs) and global gene expression in 38 GC samples from old and young patients. We identified frequent CNAs, which included copy number gains on chromosomes 3q, 7p, 8q, 20p, and 20q and copy number losses on chromosomes 19p and 21p. The most frequently gained region was 7p21.1 (55%), whereas the most frequently deleted region was 21p11.1 (50%). Recurrent highly amplified regions 17q12 and 7q31.1-7q31.31 harbored two well-known oncogenes: ERBB2 and MET. Correlation analysis of CNAs and gene expression levels identified CAPZA2 (co-amplified with MET) and genes GRB7, MIEN1, PGAP3, and STARD3 (co-amplified with ERBB2) as potential candidate cancer-promoting genes (CPGs). Public dataset analysis confirmed co-amplification of these genes with MET or ERBB2 in GC tissue samples, and revealed that high expression (except for PGAP3) was significantly associated with shorter overall survival. Knockdown of these genes using small interfering RNA led to significant suppression of GC cell proliferation and migration. Reduced GC cell proliferation mediated by CAPZA2 knockdown was attributable to attenuated cell cycle progression and increased apoptosis. This study identified novel candidate CPGs co-amplified with MET or ERBB2, and suggests that they play a functional role in GC. Impact Journals LLC 2017-09-21 /pmc/articles/PMC5696175/ /pubmed/29190909 http://dx.doi.org/10.18632/oncotarget.21150 Text en Copyright: © 2017 Kwon et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Kwon, Mi Jeong
Kim, Ryong Nam
Song, Kyoung
Jeon, Sinyoung
Jeong, Hae Min
Kim, Joo Seok
Han, Jinil
Hong, Sungyoul
Oh, Ensel
Choi, Jong-Sun
An, Jungsuk
Pollack, Jonathan R.
Choi, Yoon-La
Park, Cheol-Keun
Shin, Young Kee
Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in gastric cancer
title Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in gastric cancer
title_full Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in gastric cancer
title_fullStr Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in gastric cancer
title_full_unstemmed Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in gastric cancer
title_short Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in gastric cancer
title_sort genes co-amplified with erbb2 or met as novel potential cancer-promoting genes in gastric cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696175/
https://www.ncbi.nlm.nih.gov/pubmed/29190909
http://dx.doi.org/10.18632/oncotarget.21150
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