Li-Chang Hector H, Kasaian Katayoon, Ng Ying, Lum Amy, Kong Esther, Lim Howard, Jones Steven Jm, Huntsman David G, Schaeffer David F, Yip Stephen
University of British Columbia, Vancouver, Canada.
Division of Anatomic Pathology, Department of Pathology and Laboratory Medicine, Vancouver General Hospital, 855 12 Ave W, Vancouver, BC, V5Z 1 M9, Canada.
BMC Cancer. 2015 Feb 6;15:32. doi: 10.1186/s12885-015-1021-7.
Adenocarcinomas of both the gastroesophageal junction and stomach are molecularly complex, but differ with respect to epidemiology, etiology and survival. There are few data directly comparing the frequencies of single nucleotide mutations in cancer-related genes between the two sites. Sequencing of targeted gene panels may be useful in uncovering multiple genomic aberrations using a single test.
DNA from 92 gastroesophageal junction and 75 gastric adenocarcinoma resection specimens was extracted from formalin-fixed paraffin-embedded tissue. Targeted deep sequencing of 46 cancer-related genes was performed through emulsion PCR followed by semiconductor-based sequencing. Gastroesophageal junction and gastric carcinomas were contrasted with respect to mutational profiles, immunohistochemistry and in situ hybridization, as well as corresponding clinicopathologic data.
Gastroesophageal junction carcinomas were associated with younger age, more frequent intestinal-type histology, more frequent p53 overexpression, and worse disease-free survival on multivariable analysis. Among all cases, 145 mutations were detected in 31 genes. TP53 mutations were the most common abnormality detected, and were more common in gastroesophageal junction carcinomas (42% vs. 27%, p = 0.036). Mutations in the Wnt pathway components APC and CTNNB1 were more common among gastric carcinomas (16% vs. 3%, p = 0.006), and gastric carcinomas were more likely to have ≥3 driver mutations detected (11% vs. 2%, p = 0.044). Twenty percent of cases had potentially actionable mutations identified. R132H and R132C missense mutations in the IDH1 gene were observed, and are the first reported mutations of their kind in gastric carcinoma.
Panel sequencing of routine pathology material can yield mutational information on several driver genes, including some for which targeted therapies are available. Differing rates of mutations and clinicopathologic differences support a distinction between adenocarcinomas that arise in the gastroesophageal junction and those that arise in the stomach proper.
胃食管交界腺癌和胃癌在分子层面都很复杂，但在流行病学、病因学和生存率方面存在差异。关于这两个部位癌症相关基因中单核苷酸突变频率的直接比较数据很少。靶向基因panel测序可能有助于通过一次检测发现多个基因组畸变。
从福尔马林固定石蜡包埋组织中提取92例胃食管交界腺癌和75例胃癌切除标本的DNA。通过乳液PCR随后进行基于半导体的测序，对46个癌症相关基因进行靶向深度测序。比较胃食管交界癌和胃癌的突变谱、免疫组化和原位杂交，以及相应的临床病理数据。
胃食管交界癌与较年轻的年龄、更频繁的肠型组织学、更频繁的p53过表达相关，多变量分析显示无病生存期较差。在所有病例中，31个基因检测到145个突变。TP53突变是检测到的最常见异常，在胃食管交界癌中更常见（42%对27%，p = 0.036）。Wnt通路成分APC和CTNNB1的突变在胃癌中更常见（16%对3%，p = 0.006），胃癌更可能检测到≥3个驱动突变（11%对2%，p = 0.044）。20%的病例鉴定出潜在可操作的突变。观察到IDH1基因中的R132H和R132C错义突变，这是胃癌中首次报道的此类突变。
常规病理材料的panel测序可以产生关于几个驱动基因的突变信息，包括一些有靶向治疗可用的基因。不同的突变率和临床病理差异支持区分胃食管交界处发生的腺癌和胃体部发生的腺癌。
