Nicoś Marcin, Krawczyk Paweł, Jarosz Bożena, Sawicki Marek, Trojanowski Tomasz, Milanowski Janusz
Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Jaczewskiego 8, 20-954, Lublin, Poland.
Pathological Laboratory, Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, 20-954, Lublin, Poland.
Brain Tumor Pathol. 2017 Jan;34(1):36-41. doi: 10.1007/s10014-016-0276-2. Epub 2017 Jan 17.
Somatic mutations in NRAS, PTEN and AKT1 genes are rarely (~1%) reported in primary NSCLC, but their role in carcinogenesis have been proven. Therefore, we assessed the frequency of them in 145 FFPE tissue samples from CNS metastases of NSCLC using the real-time PCR technique. We identified four (two NRAS and single AKT1 and PTEN) mutations in CNS metastases of NSCLC. All mutations were observed in current male smokers (4% out of the male group; 4/100 and 4.25% out of smokers; 4/94). Three mutations have been detected in patients with SqCC (10.3% out of SqCC patients; 3/29), and only one mutation in the NRAS gene-in a patient with adenocarcinoma (1.25% out of AC patients; 1/80). The examined genes were mutually exclusive in terms of molecular background in KRAS; EGFR; DDR2; PIK3CA; HER2 and MEK1 genes that were evaluated in our previous studies. The OS of the patients who harbored NRAS, AKT1 and PTEN mutations was 10.1, 12.1, 7.3 and 4 months, respectively (vs 13.5 months of the studied group). Our results suggest that the presence of NRAS, PTEN and AKT1 gene mutations may have an influence on the occurrence of CNS metastases in patients with SqCC.
NRAS、PTEN和AKT1基因的体细胞突变在原发性非小细胞肺癌中报道较少（约1%），但其在致癌过程中的作用已得到证实。因此，我们使用实时PCR技术评估了145份来自非小细胞肺癌中枢神经系统转移灶的福尔马林固定石蜡包埋（FFPE）组织样本中这些突变的频率。我们在非小细胞肺癌中枢神经系统转移灶中鉴定出4个突变（2个NRAS突变以及单个AKT1和PTEN突变）。所有突变均在当前的男性吸烟者中观察到（占男性组的4%；100人中的4人；占吸烟者的4.25%；94人中的4人）。在鳞状细胞癌（SqCC）患者中检测到3个突变（占SqCC患者的10.3%；29人中的3人），而在腺癌（AC）患者中仅在NRAS基因中检测到1个突变（占AC患者的1.25%；80人中的1人）。在所检测的基因中，就KRAS、EGFR、DDR2、PIK3CA、HER2和MEK1基因的分子背景而言，它们是相互排斥的，这些基因在我们之前的研究中已进行评估。携带NRAS、AKT1和PTEN突变的患者的总生存期分别为10.1、12.1、7.3和4个月（而研究组为13.5个月）。我们的结果表明，NRAS、PTEN和AKT1基因突变的存在可能对SqCC患者中枢神经系统转移的发生有影响。
