Jia Feifei, Teer Jamie K, Knepper Todd C, Lee Jae K, Zhou Hong-Hao, He Yi-Jing, McLeod Howard L
Institute for Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
Division of Population Science, DeBartolo Family Personalized Medicine Institute, Moffitt Cancer Center, Tampa, FL, USA.
Mol Diagn Ther. 2017 Apr;21(2):179-185. doi: 10.1007/s40291-016-0250-z.
Differences in response to cancer treatments have been observed among racially and ethnically diverse gastric cancer (GC) patient populations. In the era of targeted therapy, mutation profiling of cancer is a crucial aspect of making therapeutic decisions. Mapping driver gene mutations for the GC patient population as a whole has significant potential to advance precision therapy.
GC patients with sequencing data (N = 473) were obtained from The Cancer Genome Atlas (TCGA; n = 295), Moffitt Cancer Center Total Cancer Care™ (TCC; n = 33), and three published studies (n = 145). In addition, relevant somatic mutation frequency data were obtained from cBioPortal, the TCC database, and an in-house analysis tool, as well as relevant publications.
We found that the somatic mutation rates of several driver genes vary significantly between GC patients of Asian and Caucasian descent, with substantial variation across different geographic regions. Non-parametric statistical tests were performed to examine the significant differences in protein-altering somatic mutations between Asian and Caucasian GC patient groups. The frequencies of somatic mutations of five genes were: APC (Asian: Caucasian 6.06 vs. 14.40%, p = 0.0076), ARIDIA (20.7 vs. 32.1%, p = 0.01), KMT2A (4.04 vs. 12.35%, p = 0.003), PIK3CA (9.6 vs. 18.52%, p = 0.01), and PTEN (2.52 vs. 9.05%, p = 0.008), showing significant differences between Asian and Caucasian GC patients.
Our study found significant differences in protein-altering somatic mutation frequencies in diverse geographic populations. In particular, we found that the somatic patterns may offer better insight and important opportunities for both targeted drug development and precision therapeutic strategies between Asian and Caucasian GC patients.
在不同种族和族裔的胃癌（GC）患者群体中，已观察到对癌症治疗的反应存在差异。在靶向治疗时代，癌症的突变谱分析是做出治疗决策的关键环节。绘制整个GC患者群体的驱动基因突变图谱对于推进精准治疗具有巨大潜力。
从癌症基因组图谱（TCGA；n = 295）、莫菲特癌症中心全癌关爱计划（TCC；n = 33）以及三项已发表的研究（n = 145）中获取有测序数据的GC患者。此外，还从cBioPortal、TCC数据库、一个内部分析工具以及相关出版物中获取了相关的体细胞突变频率数据。
我们发现，亚洲和白种人后裔的GC患者中，几个驱动基因的体细胞突变率存在显著差异，不同地理区域之间也有很大差异。进行了非参数统计检验，以检查亚洲和白种人GC患者组之间蛋白质改变性体细胞突变的显著差异。五个基因的体细胞突变频率分别为：APC（亚洲人：白种人6.06% 对14.40%，p = 0.0076）、ARIDIA（20.7% 对32.1%，p = 0.01）、KMT2A（4.04% 对12.35%，p = 0.003）、PIK3CA（9.6% 对18.52%，p = 0.01）和PTEN（2.52% 对9.05%，p = 0.008），显示亚洲和白种人GC患者之间存在显著差异。
我们的研究发现不同地理人群中蛋白质改变性体细胞突变频率存在显著差异。特别是，我们发现体细胞模式可能为亚洲和白种人GC患者的靶向药物开发和精准治疗策略提供更好的见解和重要机遇。
