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基于阵列比较基因组杂交技术的胃原位癌和腺瘤的基因组分析。

Genomic profiling of gastric carcinoma in situ and adenomas by array-based comparative genomic hybridization.

机构信息

Department of Molecular Pathology, Oita University, Oita, Japan.

出版信息

J Pathol. 2010 May;221(1):96-105. doi: 10.1002/path.2686.

Abstract

Although genomic copy number aberrations (CNAs) of gastric carcinoma at the advanced stage have already been extensively characterized by array comparative genomic hybridization (array CGH) analysis, those of gastric carcinoma in situ (CIS) are still poorly understood. Furthermore, no reports have demonstrated correlations between CNAs and histopathological features of gastric adenoma. In this study, we investigated CNAs of 20 gastric CISs (Vienna category 4.2) and 20 adenomas including seven low-grade adenomas (LGA; Vienna category 3) and 13 high-grade adenomas (HGA; Vienna category 4.1), using oligonucleotide-based array CGH. The most frequent aberrations in CIS were gains at 8q (85%) and 20q (50%), and losses at 5q (50%) and 17p (50%), suggesting that these CNAs are involved in the development of CIS. We found that the pattern of CNAs in HGA was quite different from that in LGA. The most frequent CNAs in HGA were gains at 8q (62%) and 7pq (54%), whereas those in LGA were gain at 7q21.3-q22.1 (57%) and loss at 5q (43%). Interestingly, gains at 8q and 7pq, both of which occurred most frequently in HGA, were not detected in any cases of LGA. Of note, 8q gain was detected most frequently in both HGA and CIS but was undetected in LGA. Since HGA is believed to have a higher risk of progression to invasive carcinoma than LGA, these data suggest that 8q gain is important for the malignant transformation of gastric adenoma.

摘要

虽然高级别胃癌的基因组拷贝数异常(CNAs)已经通过 array 比较基因组杂交(array CGH)分析得到了广泛的描述,但原位胃癌(CIS)的 CNAs 仍然知之甚少。此外,目前尚无报道表明 CNAs 与胃腺瘤的组织病理学特征之间存在相关性。在这项研究中,我们使用寡核苷酸 array CGH 分析了 20 例胃癌 CIS(维也纳分类 4.2)和 20 例腺瘤,包括 7 例低级别腺瘤(LGA;维也纳分类 3)和 13 例高级别腺瘤(HGA;维也纳分类 4.1)。CIS 中最常见的异常是 8q(85%)和 20q(50%)的增益,以及 5q(50%)和 17p(50%)的缺失,表明这些 CNA 参与了 CIS 的发生。我们发现 HGA 中的 CNA 模式与 LGA 有很大的不同。HGA 中最常见的 CNA 是 8q(62%)和 7pq(54%)的增益,而 LGA 中最常见的 CNA 是 7q21.3-q22.1(57%)的增益和 5q(43%)的缺失。有趣的是,在 HGA 中最常发生的 8q 和 7pq 的增益在任何 LGA 病例中均未检测到。值得注意的是,8q 增益在 HGA 和 CIS 中均最常被检测到,但在 LGA 中未被检测到。由于 HGA 被认为比 LGA 更有可能进展为浸润性癌,这些数据表明 8q 增益对于胃腺瘤的恶性转化很重要。

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