阿拉伯结直肠癌患者中KRAS、NRAS、BRAF、PIK3CA、AKT1和FBXW7体细胞基因突变的分子谱：频率和分布模式的确定
Molecular spectrum of , , , , , and somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern.
作者信息
Al-Shamsi Humaid O, Jones Jeremy, Fahmawi Yazan, Dahbour Ibrahim, Tabash Aziz, Abdel-Wahab Reham, Abousamra Ahmed O S, Shaw Kenna R, Xiao Lianchun, Hassan Manal M, Kipp Benjamin R, Kopetz Scott, Soliman Amr S, McWilliams Robert R, Wolff Robert A
机构信息
Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA;; Khalifa Bin Zayed Al Nahyan Foundation, Abu Dhabi, United Arab Emirates;; Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.
出版信息
J Gastrointest Oncol. 2016 Dec;7(6):882-902. doi: 10.21037/jgo.2016.11.02.
BACKGROUND
The frequency rates of mutations such as and in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features.
METHODS
Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed. The mutation rates of and were recorded, along with clinicopathological features. Other somatic mutation and their rates were also identified. Fisher's exact test was used to determine the association between mutation status and clinical features.
RESULTS
A total of 198 cases were identified; 99 Arab patients and 99 Western patients. Fifty-two point seven percent of Arab patients had stage IV disease at initial presentation, 74.2% had left-sided tumors. Eighty-nine point two percent had tubular adenocarcinoma and 10.8% had mucinous adenocarcinoma. The prevalence rates of mutations in Arab population were 44.4%, 4%, 4%, 13.1%, 52.5%, 27.3%, 2% and 3% respectively. Compared to 48.4%, 4%, 4%, 12.1%, 47.5%, 24.2%, 11.1% and 0% respectively in matched Western population. Associations between these mutations and patient clinicopathological features were not statistically significant.
CONCLUSIONS
This is the first study to report comprehensive hotspot mutations using NGS in Arab patients with CRC. The frequency of and mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of mutation.
背景
结直肠癌（CRC）中诸如 和 等突变的频率在不同人群中存在差异。本研究的目的是评估阿拉伯人群中的突变频率，并确定它们与某些临床病理特征的相关性。
方法
确定并回顾性分析来自阿拉伯海湾地区的阿拉伯患者以及年龄和性别匹配的西方CRC患者群体，这些患者的肿瘤通过下一代测序（NGS）进行评估。记录 和 的突变率以及临床病理特征。还确定了其他体细胞突变及其发生率。使用Fisher精确检验来确定突变状态与临床特征之间的关联。
结果
共确定了198例病例；99例阿拉伯患者和99例西方患者。52.7%的阿拉伯患者初诊时为IV期疾病，74.2%为左侧肿瘤。89.2%为管状腺癌，10.8%为黏液腺癌。阿拉伯人群中 突变的发生率分别为44.4%、4%、4%、13.1%、52.5%、27.3%、2%和3%。相比之下，匹配的西方人群中分别为48.4%、4%、4%、12.1%、47.5%、24.2%、11.1%和0%。这些突变与患者临床病理特征之间的关联无统计学意义。
结论
这是第一项使用NGS报告阿拉伯CRC患者全面热点突变的研究。 和 突变的频率与西方人群中报告的频率相似，除了SMAD4突变频率较低而 突变频率较高。
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