Genomic profiling of submucosal-invasive gastric cancer by array-based comparative genomic hybridization.

Genomic copy number aberrations (CNAs) in gastric cancer have already been extensively characterized by array comparative genomic hybridization (array CGH) analysis. However, involvement of genomic CNAs in the process of submucosal invasion and lymph node metastasis in early gastric cancer is still...

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Main Authors: Akiko Kuroda, Yoshiyuki Tsukamoto, Lam Tung Nguyen, Tsuyoshi Noguchi, Ichiro Takeuchi, Masahiro Uchida, Tomohisa Uchida, Naoki Hijiya, Chisato Nakada, Tadayoshi Okimoto, Masaaki Kodama, Kazunari Murakami, Keiko Matsuura, Masao Seto, Hisao Ito, Toshio Fujioka, Masatsugu Moriyama
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3141024?pdf=render
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author Akiko Kuroda
Yoshiyuki Tsukamoto
Lam Tung Nguyen
Tsuyoshi Noguchi
Ichiro Takeuchi
Masahiro Uchida
Tomohisa Uchida
Naoki Hijiya
Chisato Nakada
Tadayoshi Okimoto
Masaaki Kodama
Kazunari Murakami
Keiko Matsuura
Masao Seto
Hisao Ito
Toshio Fujioka
Masatsugu Moriyama
author_facet Akiko Kuroda
Yoshiyuki Tsukamoto
Lam Tung Nguyen
Tsuyoshi Noguchi
Ichiro Takeuchi
Masahiro Uchida
Tomohisa Uchida
Naoki Hijiya
Chisato Nakada
Tadayoshi Okimoto
Masaaki Kodama
Kazunari Murakami
Keiko Matsuura
Masao Seto
Hisao Ito
Toshio Fujioka
Masatsugu Moriyama
author_sort Akiko Kuroda
collection DOAJ
description Genomic copy number aberrations (CNAs) in gastric cancer have already been extensively characterized by array comparative genomic hybridization (array CGH) analysis. However, involvement of genomic CNAs in the process of submucosal invasion and lymph node metastasis in early gastric cancer is still poorly understood. In this study, to address this issue, we collected a total of 59 tumor samples from 27 patients with submucosal-invasive gastric cancers (SMGC), analyzed their genomic profiles by array CGH, and compared them between paired samples of mucosal (MU) and submucosal (SM) invasion (23 pairs), and SM invasion and lymph node (LN) metastasis (9 pairs). Initially, we hypothesized that acquisition of specific CNA(s) is important for these processes. However, we observed no significant difference in the number of genomic CNAs between paired MU and SM, and between paired SM and LN. Furthermore, we were unable to find any CNAs specifically associated with SM invasion or LN metastasis. Among the 23 cases analyzed, 15 had some similar pattern of genomic profiling between SM and MU. Interestingly, 13 of the 15 cases also showed some differences in genomic profiles. These results suggest that the majority of SMGCs are composed of heterogeneous subpopulations derived from the same clonal origin. Comparison of genomic CNAs between SMGCs with and without LN metastasis revealed that gain of 11q13, 11q14, 11q22, 14q32 and amplification of 17q21 were more frequent in metastatic SMGCs, suggesting that these CNAs are related to LN metastasis of early gastric cancer. In conclusion, our data suggest that generation of genetically distinct subclones, rather than acquisition of specific CNA at MU, is integral to the process of submucosal invasion, and that subclones that acquire gain of 11q13, 11q14, 11q22, 14q32 or amplification of 17q21 are likely to become metastatic.
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spelling doaj.art-4a0c36a9fe284b03a76bbb4e4016a8f12022-12-21T17:49:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0167e2231310.1371/journal.pone.0022313Genomic profiling of submucosal-invasive gastric cancer by array-based comparative genomic hybridization.Akiko KurodaYoshiyuki TsukamotoLam Tung NguyenTsuyoshi NoguchiIchiro TakeuchiMasahiro UchidaTomohisa UchidaNaoki HijiyaChisato NakadaTadayoshi OkimotoMasaaki KodamaKazunari MurakamiKeiko MatsuuraMasao SetoHisao ItoToshio FujiokaMasatsugu MoriyamaGenomic copy number aberrations (CNAs) in gastric cancer have already been extensively characterized by array comparative genomic hybridization (array CGH) analysis. However, involvement of genomic CNAs in the process of submucosal invasion and lymph node metastasis in early gastric cancer is still poorly understood. In this study, to address this issue, we collected a total of 59 tumor samples from 27 patients with submucosal-invasive gastric cancers (SMGC), analyzed their genomic profiles by array CGH, and compared them between paired samples of mucosal (MU) and submucosal (SM) invasion (23 pairs), and SM invasion and lymph node (LN) metastasis (9 pairs). Initially, we hypothesized that acquisition of specific CNA(s) is important for these processes. However, we observed no significant difference in the number of genomic CNAs between paired MU and SM, and between paired SM and LN. Furthermore, we were unable to find any CNAs specifically associated with SM invasion or LN metastasis. Among the 23 cases analyzed, 15 had some similar pattern of genomic profiling between SM and MU. Interestingly, 13 of the 15 cases also showed some differences in genomic profiles. These results suggest that the majority of SMGCs are composed of heterogeneous subpopulations derived from the same clonal origin. Comparison of genomic CNAs between SMGCs with and without LN metastasis revealed that gain of 11q13, 11q14, 11q22, 14q32 and amplification of 17q21 were more frequent in metastatic SMGCs, suggesting that these CNAs are related to LN metastasis of early gastric cancer. In conclusion, our data suggest that generation of genetically distinct subclones, rather than acquisition of specific CNA at MU, is integral to the process of submucosal invasion, and that subclones that acquire gain of 11q13, 11q14, 11q22, 14q32 or amplification of 17q21 are likely to become metastatic.http://europepmc.org/articles/PMC3141024?pdf=render
spellingShingle Akiko Kuroda
Yoshiyuki Tsukamoto
Lam Tung Nguyen
Tsuyoshi Noguchi
Ichiro Takeuchi
Masahiro Uchida
Tomohisa Uchida
Naoki Hijiya
Chisato Nakada
Tadayoshi Okimoto
Masaaki Kodama
Kazunari Murakami
Keiko Matsuura
Masao Seto
Hisao Ito
Toshio Fujioka
Masatsugu Moriyama
Genomic profiling of submucosal-invasive gastric cancer by array-based comparative genomic hybridization.
PLoS ONE
title Genomic profiling of submucosal-invasive gastric cancer by array-based comparative genomic hybridization.
title_full Genomic profiling of submucosal-invasive gastric cancer by array-based comparative genomic hybridization.
title_fullStr Genomic profiling of submucosal-invasive gastric cancer by array-based comparative genomic hybridization.
title_full_unstemmed Genomic profiling of submucosal-invasive gastric cancer by array-based comparative genomic hybridization.
title_short Genomic profiling of submucosal-invasive gastric cancer by array-based comparative genomic hybridization.
title_sort genomic profiling of submucosal invasive gastric cancer by array based comparative genomic hybridization
url http://europepmc.org/articles/PMC3141024?pdf=render
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