PDF(Pubmed)
Abstract：
UNASSIGNED: Brain metastases derived from non-small cell lung cancer (NSCLC) represent a significant clinical problem. We aim to characterize the genomic landscape of brain metastases derived from NSCLC and assess clinical actionability.
UNASSIGNED: We searched Embase, MEDLINE, Web of Science, and BIOSIS from inception to 18/19 May 2022. We extracted information on patient demographics, smoking status, genomic data, matched primary NSCLC, and programmed cell death ligand 1 expression.
UNASSIGNED: We found 72 included papers and data on 2346 patients. The most frequently mutated genes from our data were EGFR (n = 559), TP53 (n = 331), KRAS (n = 328), CDKN2A (n = 97), and STK11 (n = 72). Common missense mutations included EGFR L858R (n = 80) and KRAS G12C (n = 17). Brain metastases of ever versus never smokers had differing missense mutations in TP53 and EGFR, except for L858R and T790M in EGFR, which were seen in both subgroups. Of the top 10 frequently mutated genes that had primary NSCLC data, we found 37% of the specific mutations assessed to be discordant between the primary NSCLC and brain metastases.
UNASSIGNED: To our knowledge, this is the first systematic review to describe the genomic landscape of brain metastases derived from NSCLC. These results provide a comprehensive outline of frequently mutated genes and missense mutations that could be clinically actionable. These data also provide evidence of differing genomic landscapes between ever versus never smokers and primary NSCLC compared to the BM. This information could have important consequences for the selection and development of targeted drugs for these patients.
UNASSIGNED: We searched Embase, MEDLINE, Web of Science, and BIOSIS from inception to 18/19 May 2022. We extracted information on patient demographics, smoking status, genomic data, matched primary NSCLC, and programmed cell death ligand 1 expression.
UNASSIGNED: We found 72 included papers and data on 2346 patients. The most frequently mutated genes from our data were EGFR (n = 559), TP53 (n = 331), KRAS (n = 328), CDKN2A (n = 97), and STK11 (n = 72). Common missense mutations included EGFR L858R (n = 80) and KRAS G12C (n = 17). Brain metastases of ever versus never smokers had differing missense mutations in TP53 and EGFR, except for L858R and T790M in EGFR, which were seen in both subgroups. Of the top 10 frequently mutated genes that had primary NSCLC data, we found 37% of the specific mutations assessed to be discordant between the primary NSCLC and brain metastases.
UNASSIGNED: To our knowledge, this is the first systematic review to describe the genomic landscape of brain metastases derived from NSCLC. These results provide a comprehensive outline of frequently mutated genes and missense mutations that could be clinically actionable. These data also provide evidence of differing genomic landscapes between ever versus never smokers and primary NSCLC compared to the BM. This information could have important consequences for the selection and development of targeted drugs for these patients.
摘要：
源自非小细胞肺癌(NSCLC)的脑转移代表了显著的临床问题。我们的目标是表征源自NSCLC的脑转移的基因组景观并评估临床可操作性。
■我们搜索了Embase,MEDLINE,WebofScience,和BIOSIS从开始到2022年5月18/19日。我们提取了病人的人口统计信息,吸烟状况,基因组数据，匹配的原发性NSCLC，和程序性细胞死亡配体1表达。
■我们发现包括2346例患者的72篇论文和数据。我们的数据中最常见的突变基因是EGFR（n=559），TP53（n=331），KRAS（n=328），CDKN2A（n=97），和STK11(n=72)。常见错义突变包括EGFRL858R(n=80)和KRASG12C(n=17)。曾经吸烟者与从未吸烟者的脑转移瘤在TP53和EGFR中有不同的错义突变，除了EGFR中的L858R和T790M，在两个亚组中都见过。在获得原发性NSCLC数据的前10个频繁突变基因中，我们发现37%的特定突变被评估为原发性NSCLC和脑转移不一致.
■据我们所知，这是对非小细胞肺癌脑转移的基因组前景进行的首次系统性综述.这些结果提供了可能在临床上可行的频繁突变的基因和错义突变的全面概述。这些数据还提供了与BM相比，从未吸烟者和原发性NSCLC之间基因组景观不同的证据。这些信息可能对这些患者的靶向药物的选择和开发产生重要影响。
■我们搜索了Embase,MEDLINE,WebofScience,和BIOSIS从开始到2022年5月18/19日。我们提取了病人的人口统计信息,吸烟状况,基因组数据，匹配的原发性NSCLC，和程序性细胞死亡配体1表达。
■我们发现包括2346例患者的72篇论文和数据。我们的数据中最常见的突变基因是EGFR（n=559），TP53（n=331），KRAS（n=328），CDKN2A（n=97），和STK11(n=72)。常见错义突变包括EGFRL858R(n=80)和KRASG12C(n=17)。曾经吸烟者与从未吸烟者的脑转移瘤在TP53和EGFR中有不同的错义突变，除了EGFR中的L858R和T790M，在两个亚组中都见过。在获得原发性NSCLC数据的前10个频繁突变基因中，我们发现37%的特定突变被评估为原发性NSCLC和脑转移不一致.
■据我们所知，这是对非小细胞肺癌脑转移的基因组前景进行的首次系统性综述.这些结果提供了可能在临床上可行的频繁突变的基因和错义突变的全面概述。这些数据还提供了与BM相比，从未吸烟者和原发性NSCLC之间基因组景观不同的证据。这些信息可能对这些患者的靶向药物的选择和开发产生重要影响。
