METHODS: This study included 25 consecutive patients with BM and 52 patients with LM from Guangdong Sanjiu Brain Hospital. All participants underwent 168-target panel sequencing.
RESULTS: Among the 25 patients with BM, TP53 was the most frequently mutated gene (44%), followed by driver genes such as EGFR and BRAF (40% and 20%, respectively). In patients with BM, EGFR_amp and CDK4 were also frequently mutated, with rates of 20% and 16%, respectively. The genetic landscape of patients with LM differed, with the top mutated genes being EGFR, TP53, EGFR_amp, CDKN2A, CCNE1, CDK4, PMS2, and PIK3CA, with mutation rates of 77%, 69%, 31%, 29%, 13%, 13%, 13%, and 12%, respectively. In our study, patients with LM exhibited significantly worse OS compared to those with BM (p = 0.029). The mutation rates of TP53, EGFR_amp, and CDKN2A varied between patients with LM and those with BM, at 69.23% vs. 44%, 30.77% vs. 20%, and 28.85% vs. 12%, respectively. Further exploration revealed that patients with BM with TP53 mutations had a shorter OS than patients without TP53 mutations (p = 0.014). Similarly, patients with LM and TP53 mutations presented with worse OS than those without TP53 mutations (p = 0.0067). LM patients with CDKN2A deletions had worse OS than those without CDKN2A deletions (p = 0.037). Additionally, patients with EGFR_amp had a shorter OS than those without EGFR_amp (p = 0.044).
CONCLUSIONS: Patients with LM exhibited significantly worse OS than those with BM. Gene signatures, such as TP53, EGFR_amp, and CDKN2A, may account for shorter outcomes in patients with LM.
方法:本研究纳入广东省三九脑科医院连续25例BM患者和52例LM患者。所有参与者都进行了168个目标组测序。
结果:在25例BM患者中,TP53是最常见的突变基因(44%),其次是EGFR和BRAF等驱动基因(40%和20%,分别)。在BM患者中,EGFR_amp和CDK4也经常发生突变,20%和16%的比率,分别。LM患者的遗传景观不同,最重要的突变基因是EGFR,TP53,EGFR_amp,CDKN2A,CCNE1、CDK4、PMS2和PIK3CA,突变率为77%,69%,31%,29%,13%,13%,13%,12%,分别。在我们的研究中,与BM患者相比,LM患者的OS显著更差(p=0.029).TP53、EGFR_amp、CDKN2A在LM患者和BM患者之间有所不同,在69.23%与44%,30.77%与20%,和28.85%与12%,分别。进一步的研究发现,具有TP53突变的BM患者的OS比没有TP53突变的患者短(p=0.014)。同样,有LM和TP53突变的患者的OS比没有TP53突变的患者差(p=0.0067).有CDKN2A缺失的LM患者的OS比没有CDKN2A缺失的患者差(p=0.037)。此外,EGFR_amp患者的OS比无EGFR_amp患者短(p=0.044).
结论:LM患者的OS明显低于BM患者。基因特征,如TP53,EGFR_amp,和CDKN2A,可能是LM患者预后较短的原因。