The potential utility of re-mining results of somatic mutation testing: KRAS status in lung adenocarcinoma.
The potential utility of re-mining results of somatic mutation testing: KRAS status in lung adenocarcinoma.
复制标题
DOI：
10.1016/j.cancergen.2016.03.001
复制
发表时间：
2016-05
期刊：
影响因子：
1.9
通讯作者：
Tsongalis GJ
中科院分区：
文献类型：
--
作者：
Biernacka A;Tsongalis PD;Peterson JD;de Abreu FB;Black CC;Gutmann EJ;Liu X;Tafe LJ;Amos CI;Tsongalis GJ
KRAS突变的非小细胞肺癌(NSCLC)的临床结果取决于存在哪种特定的KRAS突变。较短的无进展生存期与KRAS变异体G12C和G12V有关。具有这些变异的细胞系在更大程度上依赖于RAS/RAF/MEK/ERK信号通路，并变得更容易受到MEK抑制。由于不同的KRAS突变可能导致药物敏感性的改变，我们的目标是在我们机构的一名NSCLC患者队列中确定特定的KRAS突变状态。使用50基因AmpliSeq™癌症热点小组v2(CHPv2)对502例非小细胞肺癌样本进行体细胞突变筛查。然而，这项研究只包括KRAS基因变异阳性的样本。在KRAS基因中确定的变异体是使用公开的数据库进行管理的。KRAS基因总突变率为32.7%(164/502)。最常见的KRAS突变是G12C(41%)、G12V(19%)和G12D(14%)，以及不太常见的变异。在重新挖掘我们的测序数据后，我们发现超过一半的KRAS突变NSCLC患者可能受益于在标准化疗药物中添加MEK抑制剂，如selumetinib。由于KRAS突变，这些患者可能无法接受传统的抗EGFR治疗，但有资格接受新的联合治疗。
KRAS mutant non-small cell lung cancers (NSCLCs) vary in clinical outcome depending on which specific KRAS mutation is present. Shorter progression free survival has been associated with KRAS variants G12C and G12V. Cell lines with these variants depend to a greater extent on the RAS/RAF/MEK/ERK signaling pathway and become more susceptible to MEK inhibition. Because different KRAS mutations may lead to altered drug sensitivity, we aimed to determine specific KRAS mutation status in a NSCLC patient cohort at our institution. A total of 502 NSCLC samples were screened for somatic mutations using the 50 gene AmpliSeq™ Cancer Hotspot Panel v2 (CHPv2). However only samples positive for variants in the KRAS gene were included in this study. Variants identified in the KRAS genes were curated using publicly available databases. The overall mutation rate in the KRAS gene was 32.7% (164/502). The most common KRAS mutations were G12C (41%), G12V (19%), and G12D (14%) along with less frequent variants. After re-mining our sequencing data, we found that more than a half of our KRAS mutant NSCLC patients could potentially benefit from the addition of a MEK inhibitor such as selumetinib to standard chemotherapeutic agents. Due to mutated KRAS, these patients will likely fail traditional anti-EGFR therapies but be eligible for newer combination therapies.
登录
查看更多内容
DOI：
10.1016/j.lungcan.2015.11.004
发表时间：
2016-02
期刊：
Lung cancer (Amsterdam, Netherlands)
影响因子：
--
作者：
Hames ML;Chen H;Iams W;Aston J;Lovly CM;Horn L
通讯作者：
Horn L
DOI：
10.1038/nrm3255
发表时间：
2011-12-22
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
28.2
作者：
Kim ES;Herbst RS;Wistuba II;Lee JJ;Blumenschein GR Jr;Tsao A;Stewart DJ;Hicks ME;Erasmus J Jr;Gupta S;Alden CM;Liu S;Tang X;Khuri FR;Tran HT;Johnson BE;Heymach JV;Mao L;Fossella F;Kies MS;Papadimitrakopoulou V;Davis SE;Lippman SM;Hong WK
通讯作者：
Hong WK
影响因子：
8.4
作者：
Cserepes, Mihaly;Ostoros, Gyula;Dome, Balazs
通讯作者：
Dome, Balazs
影响因子：
20.4
作者：
Riely, Gregory J.;Johnson, Melissa L.;Ginsberg, Michelle S.
通讯作者：
Ginsberg, Michelle S.