Abstract:
BRAF V600E and KRAS mutations that occur in colorectal cancer (CRC) define a subpopulation of patients with an inferior prognosis. Recently, the first BRAF V600E-targeting therapy has been approved and novel agents targeting KRAS G12C are being evaluated in CRC. A better understanding of the clinical characteristics of the populations defined by those mutations is needed. We created a retrospective database that collects clinical characteristics of patients with metastatic CRC evaluated for RAS and BRAF mutations in a single laboratory. A total of 7604 patients tested between October 2017 and December 2019 were included in the analysis. The prevalence of BRAF V600E was 6.77%. Female sex, primary in the right colon, high-grade, mucinous, signet cell, partially neuroendocrine histology, perineural and vascular invasion, and surgical tissue sample were factors associated with increased mutation rates. The prevalence of KRAS G12C was 3.11%. Cancer of primary origin in the left colon and in samples from brain metastases were associated with increased mutation rates. The high prevalence of the BRAF V600E mutation in cancers with a neuroendocrine component identifies a potential candidate population for BRAF inhibition. The association of KRAS G12C with the left part of the intestine and brain metastases of CRC are new findings and require further investigation.
摘要:
在结直肠癌(CRC)中发生的BRAFV600E和KRAS突变定义了预后较差的患者亚群。最近,首个BRAFV600E靶向治疗已获得批准,针对KRASG12C的新型药物正在CRC中进行评估.需要更好地了解由这些突变定义的人群的临床特征。我们建立了一个回顾性数据库,收集转移性CRC患者的临床特征,在单一实验室中评估RAS和BRAF突变。在2017年10月至2019年12月期间,共有7604名患者被纳入分析。BRAFV600E的患病率为6.77%。女性性别,原发性在右结肠,高品位,粘液,图章细胞,部分神经内分泌组织学,神经周和血管侵犯,和手术组织样本是与突变率增加相关的因素。KRASG12C的患病率为3.11%。左结肠和脑转移样品中的原发性癌症与突变率增加有关。具有神经内分泌成分的癌症中BRAFV600E突变的高患病率鉴定了BRAF抑制的潜在候选群体。KRASG12C与肠左部分和CRC脑转移的相关性是新发现,需要进一步研究。