Background: To examine whether gastric carcinoma (GC) with chromosomal instability (CIN-type GC), the largest category in the Cancer Genome Atlas classification, consists of a single genetic lineage, we conducted a multisampling analysis of genomic DNA copy-number profile. Methods: We performed array-based comparative genomic hybridization using formalin-fixed paraffin-embedded tissues from 54 gland-forming GCs containing a total of 106 DNA samples from mucosal, extramucosal invasive, and lymph node lesions. Microarray data were analyzed by unsupervised hierarchical clustering and penetrance plots. Epstein-Barr virus infection status and mismatch repair (MMR) enzyme-silencing/p53/mucin expression were examined by in situ hybridization and immunohistochemistry, respectively. Results: The samples examined were divided into gain-rich cluster A and loss-rich cluster B, which were different in tumor locus and patient age. The T1/T2–4 ratio, the frequency of small cancers (diameter ≤2–4 cm), and intestinal mucin expression were higher in cluster B than in cluster A, but there were no significant differences in the frequencies of MMR silencing, mutant p53 pattern, and lymph node metastasis between the 2 clusters. Conclusions: We demonstrated that CIN-type GC could be categorized into 2 genetic lineages which are different in terms of rapidity of local extension but similar in terms of nodal metastasis risk.

中文翻译：

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DNA 拷贝数谱的多重采样分析揭示了染色体不稳定型腺体形成胃癌中快速和缓慢生长的谱系

背景：为了检查具有染色体不稳定性（CIN 型 GC）（癌症基因组图谱分类中的最大类别）的胃癌 (GC) 是否由单一遗传谱系组成，我们对基因组 DNA 拷贝数谱进行了多重采样分析。方法：我们使用福尔马林固定石蜡包埋的组织进行了基于阵列的比较基因组杂交，这些组织来自 54 个腺体形成 GC，其中包含来自粘膜、粘膜外浸润性和淋巴结病变的总共 106 个 DNA 样本。通过无监督层次聚类和外显率图分析微阵列数据。Epstein-Barr 病毒感染状态和错配修复 (MMR) 酶沉默/p53/粘蛋白表达分别通过原位杂交和免疫组织化学检查。结果：检查的样本分为富含增益的簇A和富含损失的簇B，它们在肿瘤位点和患者年龄方面不同。B簇中T1/T2-4比值、小癌（直径≤2-4 cm）和肠粘蛋白表达的频率高于簇A，但MMR沉默、突变的频率没有显着差异p53 模式，以及 2 个簇之间的淋巴结转移。结论：我们证明 CIN 型 GC 可以分为 2 种遗传谱系，它们在局部扩展的速度方面不同，但在淋巴结转移风险方面相似。但在 MMR 沉默、突变 p53 模式和 2 个簇之间的淋巴结转移频率上没有显着差异。结论：我们证明 CIN 型 GC 可以分为 2 种遗传谱系，它们在局部扩展的速度方面不同，但在淋巴结转移风险方面相似。但在 MMR 沉默、突变 p53 模式和 2 个簇之间的淋巴结转移频率上没有显着差异。结论：我们证明 CIN 型 GC 可以分为 2 种遗传谱系，它们在局部扩展的速度方面不同，但在淋巴结转移风险方面相似。