ORAOV1 is a probable target within the 11q13.3 amplicon in lymph node metastases from gastric adenocarcinoma
ORAOV1 is a probable target within the 11q13.3 amplicon in lymph node metastases from gastric adenocarcinoma
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DOI：
10.3892/ijmm.2011.811
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发表时间：
2012-01-01
影响因子：
5.4
通讯作者：
Koo, Sun Hoe
中科院分区：
文献类型：
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作者：
Kang, Ji Un;Koo, Sun Hoe
肿瘤细胞的淋巴结转移（LNM）扩散是癌症扩散初始过程中的常见事件，是胃腺癌（GAC）强有力的独立预后指标。进行高密度基因组阵列以确定与 GAC 淋巴结转移相关的分子标记。在全基因组谱中，涉及染色体 1p、3q、8q、9q、11q、16p、19p 和 20q（对数，比率 >0.25）（>40% 的患者）的大拷贝数增加比拷贝数丢失更为普遍。最显着的发现是 11 号染色体长臂的拷贝数增加，这发生在 75.0% 的淋巴转移 GAC 病例中，所描绘的最小共同区域是 11q24.2-q12.1。更具体地说，在 12.5% 的病例中检测到 11q13.3 区域有 2 个扩增（>1 log(2) 比率）基因座。第一个基因座覆盖类似于 7.7 Mbp 的区域，包含代表性癌基因细胞周期蛋白 D1 (CCNDI)。这一发现发生在 12.5% 的病例中。此外，口腔癌过度表达 1 (ORAOV1) 基因被确定为 11q13 扩增子内的可能靶标，此前人们认为该基因不会在 GAC 中发挥致病作用 (12.5%)。 11q13.3 上跨 7.8 Mbp 且无相关基因的第二个基因座也在 12.5% 的 GAC 中显示出高水平扩增。这项研究表明，11 号染色体的长臂含有与淋巴转移形成相关的原癌基因，而 11q13.3 区域的 ORAOV1 基因可能是一个潜在的靶点，并可作为 GAC 中隐匿性转移存在的指标。
The lymph node metastatic (LNM) spread of tumor cells is a frequent event in the initial process of cancer dissemination and is a powerful independent prognostic indicator in gastric adenocarcinoma (GAC). High density genomic arrays were conducted to identify molecular markers associated with lymph node metastasis in GAC. In the genome-wide profile, large copy number gains involving chromosomes 1p, 3q, 8q, 9q, 11q, 16p, 19p, and 20q (log, ratio >0.25) (>40% of patients) were more prevalent than copy number losses. The most notable finding was copy number gains at the long arm of chromosome 11, which occurred in 75.0% of lymphatic metastasis GAC cases, and the delineated minimal common region was 11q24.2-q12.1. More specifically, 2 amplified (>1 log(2) ratio) loci on the 11q13.3 region were detected in 12.5% of the cases. The first locus, covers a region of similar to 7.7 Mbp, and comprises the representative oncogene of cyclin D1 (CCNDI). This finding occurred in 12.5% of the cases. Additionally, an oral cancer overexpressed 1 (ORAOV1) gene was identified as a probable target within the 11q13 amplicon, which previously was not assumed to play a pathogenic role in GACs (12.5%). A second locus spanning 7.8 Mbp on 11q13.3 without associated genes also showed high-level amplifications in 12.5% of the GACs. This study indicates that the long arm of chromosome 11 harbors protooncogenes that are associated with lymphatic metastasis formation and the ORAOV1 gene at the 11q13.3 region could be a potential target and serve as an indicator for the presence of occult metastases in GAC.