Early and advanced gastric cancer genomes. Homo sapiens

Early gastric cancers (EGC) precede advanced gastric cancers (AGC) with a favorable clinical outcome compared to advanced gastric cancers (AGC). To understand the progression mechanisms of EGC to AGC, it is required to disclose the EGC and AGC genomes in terms of the the mutational and evolutionary perspectives. In this study, we performed whole-exome sequencing and copy number profiling of nine microsatellite (MS)-unstable (MSI-H) (5 EGC and 4 AGC) and eight MS-stable (MSS) gastric cancers (4 EGC and 4 AGC). Unexpectedly, we observed no substantial differences in the number, sequence composition and functional consequences (potential driver mutations and affected pathways) of the mutations and CNAs between EGC and AGC genomes in both MSI-H and MSS cases. Overall design: Gastrectomy tissues from 17 GC patients were used for this study. The hospital pathology department confirmed pathologic features of the GC (e.g., EGC vs. AGC, differentiation, lymph node metastasis and TNM stage). All of the picked areas from tumor and normal areas were frozen, cut, and stained with hematoxylin & eosin (H&E). Two pathologists selected cases with rich tumor cell population (at least 60%), which were subsequently used in the study. Copy number profiling was performed using Agilent 180K platform according to the manufacturer's protocol.

早期胃癌（early gastric cancer, EGC）是进展期胃癌（advanced gastric cancer, AGC）的前驱病变，相较于进展期胃癌，早期胃癌的临床预后更佳。为阐明EGC向AGC进展的分子机制，需从突变与演化视角解析两类胃癌的基因组特征。
本研究对9例微卫星不稳定（microsatellite unstable, MSI-H）胃癌（含5例EGC与4例AGC）以及8例微卫星稳定（microsatellite stable, MSS）胃癌（含4例EGC与4例AGC）开展了全外显子组测序（whole-exome sequencing）与拷贝数特征分析。
出乎意料的是，无论在MSI-H还是MSS亚型中，EGC与AGC基因组的突变及拷贝数异常（copy number aberrations, CNAs）的数量、序列构成与功能影响（潜在驱动突变及受影响通路）均无显著差异。
研究整体设计：本研究纳入17例胃癌患者的胃切除术后组织样本。医院病理科确认了胃癌的病理特征，包括EGC与AGC分型、肿瘤分化程度、淋巴结转移情况及TNM分期（TNM stage）。所有选取的肿瘤与正常组织区域均经冷冻处理、切片，并进行苏木精-伊红（hematoxylin & eosin, H&E）染色。由两名病理医师筛选肿瘤细胞占比≥60%的样本，用于后续实验。拷贝数特征分析采用安捷伦180K平台（Agilent 180K platform），严格按照厂商提供的实验流程完成。