Nicoś Marcin, Powrózek Tomasz, Krawczyk Paweł, Jarosz Bożena, Pająk Beata, Sawicki Marek, Kucharczyk Krzysztof, Trojanowski Tomasz, Milanowski Janusz
Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Jaczewskiego 8, 20-954, Lublin, Poland,
Med Oncol. 2014 Oct;31(10):176. doi: 10.1007/s12032-014-0176-4. Epub 2014 Aug 31.
Discoidin death receptor 2 (DDR2) receptor belongs to a DDR family that shows a tyrosine kinase activity. The somatic mutations in DDR2 gene, reported in non-small cell lung cancer (NSCLC), are involved in up-regulation of cells' migration, proliferation and survival. A S768R substitution in DDR2 gene was commonly reported in squamous cell lung carcinoma. Clinical data of patients carrying the DDR2 gene mutation suggest that its presence can be independent of gender and age. The effectiveness of an oral dual-specific (Src and Abl) multikinase inhibitors-dasatinib-was observed in different cell lines and in some NSCLC patients with identified DDR2 mutation. In the present study, we have used three molecular methods (ASP-real-time PCR, ASP-DNA-FLA PCR and direct sequencing) to detect the DDR2 gene mutation in 143 patients with NSCLC metastases to the central nervous system (CNS). The prevalence of the DDR2 gene mutation was correlated with the occurrence of mutations in the EGFR, KRAS, HER2 and BRAF genes. We identified three patients (2.1% of studied group) with DDR2 mutation. The mutation was observed in two patients with low differentiated squamous cell lung cancer and in one patient with adeno-squamous cell carcinoma (ADSCC). In ADSCC patients, DDR2 mutation coexisted with G12C substitution in KRAS gene. According to the current knowledge, examination of the presence of the DDR2 gene mutation in metastatic lesion is the first such report worldwide. The information, that these driver mutations are present in CNS metastases of NSCLC, could broaden therapeutic choices in such group of patients.
盘状结构域受体2（DDR2）属于具有酪氨酸激酶活性的DDR家族。非小细胞肺癌（NSCLC）中报道的DDR2基因体细胞突变与细胞迁移、增殖和存活的上调有关。DDR2基因中的S768R替代在肺鳞状细胞癌中普遍报道。携带DDR2基因突变患者的临床数据表明，其存在与性别和年龄无关。在不同细胞系和一些已鉴定出DDR2突变的NSCLC患者中观察到口服双特异性（Src和Abl）多激酶抑制剂达沙替尼的有效性。在本研究中，我们使用了三种分子方法（ASP-实时PCR、ASP-DNA-FLA PCR和直接测序）来检测143例发生中枢神经系统（CNS）转移的NSCLC患者的DDR2基因突变。DDR2基因突变的发生率与EGFR、KRAS、HER2和BRAF基因的突变发生率相关。我们鉴定出3例（占研究组的2.1%）DDR2基因突变患者。在2例低分化肺鳞状细胞癌患者和1例腺鳞癌（ADSCC）患者中观察到该突变。在ADSCC患者中，DDR2突变与KRAS基因中的G12C替代共存。根据目前的知识，检测转移灶中DDR2基因突变的存在是全球首例此类报告。这些驱动突变存在于NSCLC的CNS转移灶中的信息可能会拓宽这类患者的治疗选择。
