Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern
Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern
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DOI：
10.21037/jgo.2016.11.02
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发表时间：
2016-12-01
影响因子：
2.1
通讯作者：
Wolff, Robert A.
中科院分区：
文献类型：
--
作者：
Al-Shamsi, Humaid O.;Jones, Jeremy;Wolff, Robert A.
背景：结直肠癌（CRC）中KRAS、NRAS、BRAF和PIK3CA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突变频率在阿拉伯人口，并确定其与某些临床病理features.Methods的相关性：阿拉伯患者从阿拉伯海湾地区和人口的年龄和性别匹配的西方CRC患者的肿瘤进行了评估与下一代测序（NGS）进行了鉴定和回顾性分析。记录KRAS、NRAS、BRAF、PIK3CA、TP53和APC的突变率，并结合临床病理特征进行沿着。还鉴定了其他体细胞突变及其发生率。Fisher精确检验被用来确定突变状态和临床feature.Results之间的关联：共确定了198例，99名阿拉伯患者和99名西方患者。52.7%的阿拉伯患者在初次就诊时患有IV期疾病，74.2%患有左侧肿瘤。管状腺癌占89.2%，粘液腺癌占10.8%。阿拉伯人群KRAS、NRAS、BRAF、PIK3CA、TP53、APC、SMAD、FBXW7基因突变的检出率分别为44.4%、4%、4%、13.1%、52.5%、27.3%、2%和3%。而西方人群分别为48.4%、4%、4%、12.1%、47.5%、24.2%、11.1%和0%。这些突变和患者的临床病理特征之间的关联没有统计学意义。结论：这是第一个研究报告全面的热点突变使用NGS在阿拉伯CRC患者。KRAS、NRAS、BRAF、TP53、APC和PIK3CA突变的频率与西方人群中报告的频率相似，但SMAD 4具有较低的频率和较高的FBXW7突变频率。
Background: The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA 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 KRAS, NRAS, BRAF, PIK3CA, TP53, and APC 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 KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 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 KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation.