Barakeh Duna H, Alsolme Ebtehal, Alqubaishi Fatimah, Almutairi Amal, Alhabeeb Lamees, Al Abdulmohsen Sally, Almohsen Shahd S, Alayed Doaa, AlAnazi Sara Rashid, AlZahrani Malak, Binowayn Albandari Mohammed, AlOtaibi Sarah S, Alkhureeb Fahad A, Al Shakweer Wafa, Al-Hindi Hindi, Alassiri Ali, Robinson Heather A, Abedalthagafi Malak
Department of Pathology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
Genomics Research Department, King Fahad Medical City, Riyadh, Saudi Arabia.
Front Med (Lausanne). 2022 Nov 24;9:947456. doi: 10.3389/fmed.2022.947456. eCollection 2022.
Central nervous system (CNS) metastasis is the most common brain tumor type in adults. Compared to their primary tumors, these metastases undergo a variety of genetic changes to be able to survive and thrive in the complex tissue microenvironment of the brain. In clinical settings, the majority of traditional chemotherapies have shown limited efficacy against CNS metastases. However, the discovery of potential driver mutations, and the development of drugs specifically targeting affected signaling pathways, could change the treatment landscape of CNS metastasis. Genetic studies of brain tumors have so far focused mainly on common cancers in western populations. In this study, we performed Next Generation Sequencing (NGS) on 50 pairs of primary tumors, including but not limited to colorectal, breast, renal and thyroid tumors, along with their brain metastatic tumor tissue counterparts, from three different local tertiary centers in Saudi Arabia. We identified potentially clinically relevant mutations in brain metastases that were not detected in corresponding primary tumors, including mutations in the PI3K, CDK, and MAPK pathways. These data highlight the differences between primary cancers and brain metastases and the importance of acquiring and analyzing brain metastatic samples for further clinical management.
中枢神经系统（CNS）转移瘤是成人中最常见的脑肿瘤类型。与原发性肿瘤相比，这些转移瘤会发生多种基因变化，以便能够在大脑复杂的组织微环境中存活和生长。在临床环境中，大多数传统化疗对CNS转移瘤的疗效有限。然而，潜在驱动突变的发现以及专门针对受影响信号通路的药物开发，可能会改变CNS转移瘤的治疗格局。迄今为止，脑肿瘤的基因研究主要集中在西方人群的常见癌症上。在本研究中，我们对来自沙特阿拉伯三个不同地方三级中心的50对原发性肿瘤及其脑转移瘤组织样本进行了下一代测序（NGS），这些原发性肿瘤包括但不限于结直肠癌、乳腺癌、肾癌和甲状腺癌。我们在脑转移瘤中鉴定出了相应原发性肿瘤中未检测到的潜在临床相关突变，包括PI3K、CDK和MAPK通路中的突变。这些数据突出了原发性癌症和脑转移瘤之间的差异，以及获取和分析脑转移样本对进一步临床管理的重要性。
