Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients.,Nature Communications

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Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients.
Nature Communications ( IF 14.7 ) Pub Date : 2019-08-19 , DOI: 10.1038/s41467-019-11530-0
Ilya G Serebriiskii _{1,

2} , Caitlin Connelly ₃ , Garrett Frampton ₃ , Justin Newberg ₃ , Matthew Cooke ₃ , Vince Miller ₃ , Siraj Ali ₃ , Jeffrey S Ross _{3,

4} , Elizabeth Handorf ₅ , Sanjeevani Arora ₆ , Christopher Lieu ₇ , Erica A Golemis ₁ , Joshua E Meyer _{1,

8}

Affiliation

Colorectal cancer (CRC) is increasingly appreciated as a heterogeneous disease, with factors such as microsatellite instability (MSI), cancer subsite within the colon versus rectum, and age of diagnosis associated with specific disease course and therapeutic response. Activating oncogenic mutations in KRAS and NRAS are common in CRC, driving tumor progression and influencing efficacy of both cytotoxic and targeted therapies. The RAS mutational spectrum differs substantially between tumors arising from distinct tissues. Structure-function analysis of relatively common somatic RAS mutations in G12, Q61, and other codons is characterized by differing potency and modes of action. Here we show the mutational profile of KRAS, NRAS, and the less common HRAS in 13,336 CRC tumors, comparing the frequency of specific mutations based on age of diagnosis, MSI status, and colon versus rectum subsite. We identify mutation hotspots, and unexpected differences in mutation spectrum, based on these clinical parameters.

中文翻译：

老年和青年患者结肠癌和直肠癌中RAS突变的全面表征。

大肠癌（CRC）被越来越多地视为一种异质性疾病，其影响因素包括微卫星不稳定性（MSI），结肠与直肠内的癌症亚位点以及与特定疾病进程和治疗反应相关的诊断年龄。在CRC中，激活KRAS和NRAS的致癌突变很普遍，既推动了肿瘤的发展，又影响了细胞毒疗法和靶向疗法的疗效。在不同组织引起的肿瘤之间，RAS突变谱存在显着差异。G12，Q61和其他密码子中相对常见的体细胞RAS突变的结构功能分析的特点是效价和作用方式不同。在这里，我们显示了基于13336例CRC肿瘤的KRAS，NRAS和较不常见的HRAS的突变情况，并根据诊断年龄比较了特定突变的频率，MSI状态以及结肠与直肠亚部位。基于这些临床参数，我们确定了突变热点和突变谱中的意外差异。

更新日期：2019-08-19

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