Todorovic Balint Milena, Jelicic Jelena, Mihaljevic Biljana, Kostic Jelena, Stanic Bojana, Balint Bela, Pejanovic Nadja, Lucic Bojana, Tosic Natasa, Marjanovic Irena, Stojiljkovic Maja, Karan-Djurasevic Teodora, Perisic Ognjen, Rakocevic Goran, Popovic Milos, Raicevic Sava, Bila Jelena, Antic Darko, Andjelic Bosko, Pavlovic Sonja
Clinic for Hematology, Clinical Center of Serbia, Belgrade 11000, Serbia.
Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia.
Int J Mol Sci. 2016 May 6;17(5):683. doi: 10.3390/ijms17050683.
The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach.
已有研究表明，可能存在一种原发性中枢神经系统淋巴瘤特异性基因组特征，它与弥漫性大B细胞淋巴瘤（DLBCL）的系统性形式不同，但仍存在争议。我们使用TruSeq Amplicon癌症检测板（TSACP）对48个癌症相关基因，对19例中枢神经系统原发性DLBCL（DLBCL CNS）患者进行了研究。下一代测序（NGS）分析显示，超过80%的潜在蛋白质改变突变位于8个基因（CTNNB1、PIK3CA、PTEN、ATM、KRAS、PTPN11、TP53和JAK3）中，表明这些基因在淋巴瘤发生中可能发挥作用。TP53是所有19例患者中唯一发生突变的基因。此外，TP53和ATM基因的突变与其他分析基因中更高的突变总数相关。此外，ATM基因的突变与无事件生存期（EFS）较差相关（p = 0.036）。SMO基因突变的存在与疾病早期复发相关（p = 0.023）、无事件生存期较差（p = 0.011）和总生存期（OS）较差（p = 0.017），而PTEN基因的突变与OS较差相关（p = 0.048）。我们的研究结果表明，TP53和ATM基因可能参与原发性DLBCL CNS的分子病理生理学，而PTEN和SMO基因的突变可能影响生存期，无论初始治疗方法如何。
