Park Joonhong, Lee Sang-Il, Shin Soyoung, Hong Jang Hee, Yoo Han Mo, Kim Jeong Goo
Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Republic of Korea.
Oncol Lett. 2020 Nov;20(5):129. doi: 10.3892/ol.2020.11990. Epub 2020 Aug 20.
Gastric cancer is one of the leading causes of cancer-associated death; however, analysis of its molecular and clinical characteristics has been complicated by its histological and etiological heterogeneity. The present study aimed to estimate somatic mutation profiling in gastric cancer. To do so, targeted next-generation sequencing (NGS) was performed with the Oncomine Focus Assay to compare the clinicopathological characteristics with the mutation profiles in 50 patients with advanced gastric cancer (AGC). Among the 35 hotspot genes and 19 genes for copy number variations (CNVs), 18 single nucleotide variants (SNVs) or small insertions and deletions (14 missense and four frameshift mutations), and 10 amplifications were identified. To examine the association between mutation profiles and clinicopathological characteristics, each element of the clinicopathological characteristics was categorized into three groups: No alteration, PI3K catalytic subunit α () alterations and alterations other than . Fisher's exact test identified no statistical differences between the clinicopathological characteristics, with the exception of the Tumor-Node-Metastasis (TNM) T stage between the three groups. Cases of AGC with somatic alterations but no exhibited a significant difference in the TNM T stage compared with those with no alterations or alterations (P=0.044). In addition, AGC with alterations was categorized by Lauren's classification to the intestinal type only. The distribution of Lauren's classification in AGC with alterations was statistically different compared with AGC with alterations other than (P=0.028), but not compared with AGC with no alterations (P=0.076). In conclusion, the present study demonstrated a molecular profiling approach that identified potential molecular classifications for gastric cancer and suggested a framework for precision medicine in AGC.
胃癌是癌症相关死亡的主要原因之一；然而，其组织学和病因学的异质性使得对其分子和临床特征的分析变得复杂。本研究旨在评估胃癌的体细胞突变谱。为此，采用Oncomine Focus检测法进行靶向二代测序（NGS），以比较50例晚期胃癌（AGC）患者的临床病理特征与突变谱。在35个热点基因和19个拷贝数变异（CNV）基因中，鉴定出18个单核苷酸变异（SNV）或小插入和缺失（14个错义突变和4个移码突变）以及10个扩增。为了研究突变谱与临床病理特征之间的关联，将临床病理特征的每个要素分为三组：无改变、PI3K催化亚基α（）改变和除以外的改变。Fisher精确检验显示，除三组之间的肿瘤-淋巴结-转移（TNM）T分期外，临床病理特征之间无统计学差异。与无改变或改变的AGC病例相比，有体细胞改变但无的AGC病例在TNM T分期上有显著差异（P=0.044）。此外，有改变的AGC根据Lauren分类仅为肠型。与有除以外改变的AGC相比，有改变的AGC中Lauren分类的分布有统计学差异（P=0.028），但与无改变的AGC相比无统计学差异（P=0.076）。总之，本研究展示了一种分子谱分析方法，该方法确定了胃癌潜在的分子分类，并为AGC的精准医学提出了一个框架。
