Genomic profiling of submucosal-invasive gastric cancer by array-based comparative genomic hybridization.
Genomic profiling of submucosal-invasive gastric cancer by array-based comparative genomic hybridization.
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DOI：
10.1371/journal.pone.0022313
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Moriyama M
中科院分区：
文献类型：
--
作者：
Kuroda A;Tsukamoto Y;Nguyen LT;Noguchi T;Takeuchi I;Uchida M;Uchida T;Hijiya N;Nakada C;Okimoto T;Kodama M;Murakami K;Matsuura K;Seto M;Ito H;Fujioka T;Moriyama M
基因组拷贝数异常(CNA)已经被阵列比较基因组杂交(ARRAGE CGH)分析广泛地表征在胃癌中。然而，基因组CNAs在早期胃癌黏膜下侵袭和淋巴结转移过程中的作用尚不清楚。在这项研究中，我们收集了27例黏膜下浸润性胃癌(SMGC)患者的59例肿瘤标本，用阵列CGH分析了它们的基因组图谱，并比较了粘膜(MU)和粘膜下(SM)侵犯(23对)和SM侵犯(SM)和淋巴结(LN)转移(9对)的配对样本。最初，我们假设收购特定的中央通讯社(S)对这些过程很重要。然而，我们观察到配对的MU和SM之间以及配对的SM和LN之间的基因组DNA数量没有显著差异。此外，我们无法找到任何与SM侵袭或LN转移相关的CNA。在分析的23例病例中，有15例在SM和MU之间具有相似的基因组图谱。有趣的是，15例中有13例在基因组图谱上也表现出一些差异。这些结果表明，大多数SMGCS是由来自同一克隆起源的不同亚群组成的。比较有无LN转移的SMGCs的基因组CNA，发现转移性SMGCs中11q13、11q14、11q22、14q32的扩增和17q21扩增的频率较高，提示这些CNA与早期胃癌的LN转移有关。综上所述，我们的数据表明，在粘膜下侵袭过程中，产生遗传上不同的亚克隆，而不是在MU获得特定的CNA，是不可或缺的，获得11q13、11q14、11q22、14q32或17q21扩增的亚克隆可能会发生转移。
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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影响因子：
8
作者：
Cooke, S. L.;Ng, C. K. Y.;Melnyk, N.;Garcia, M. J.;Hardcastle, T.;Temple, J.;Langdon, S.;Huntsman, D.;Brenton, J. D.
通讯作者：
Brenton, J. D.
影响因子：
8.8
作者：
Barros-Silva, J. D.;Leitao, D.;Afonso, L.;Vieira, J.;Dinis-Ribeiro, M.;Fragoso, M.;Bento, M. J.;Santos, L.;Ferreira, P.;Rego, S.;Brandao, C.;Carneiro, F.;Lopes, C.;Schmitt, F.;Teixeira, M. R.
通讯作者：
Teixeira, M. R.
影响因子：
7.3
作者：
Maria Sayagues, Jose;del Mar Abad, Maria;Munoz-Bellvis, Luis
通讯作者：
Munoz-Bellvis, Luis
影响因子：
8
作者：
Jarvinen, A-K;Autio, R.;Monni, O.
通讯作者：
Monni, O.
影响因子：
--
作者：
Aubele, M;Mattis, A;Werner, M
通讯作者：
Werner, M