Clinicopathologic and genomic characterizations of brain metastases using a comprehensive genomic panel

• Type of Material: Article
• Authors: Malak AlThgafi, Emory University; Duna H Barakeh, King Saud University; Ebtehal Alsolme, King Fahad Medical City; Fatimah Alqubaishi, King Fahad Medical City; Amal Almutairi, King Fahad Medical City; Lamess Alhabeeb, King Fahad Medical City; Sally Al Abdulmohsen, King Fahad Medical City; Shahd S Almohsen, King Abdulaziz Medical City; Doaa Alayed, King Saud University; Sara Rashid AlAnazi, Secur Forces Hosp; Malak AlZahrani, King Saud University; Albandari Mohammed Binowayn, King Fahad Medical City; Sarah S AlOtaibi, King Fahad Medical City; Fahad A Alkhureeb, King Fahad Medical City; Wafa Al Shakweer, King Fahad Medical City; Hindi Al-Hindi, King Faisal Specialist Hospital and Research Center; Ali Alassiri, King Abdulaziz Medical City; Heather A Robinson, University of Manchester; Malak Abedalthagafi, King Fahad Medical City
• Language: English
• Date: 2022-11-24
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Barakeh, Alsolme, Alqubaishi, Almutairi, Alhabeeb, Al Abdulmohsen, Almohsen, Alayed, AlAnazi, AlZahrani, Binowayn, AlOtaibi, Alkhureeb, Al Shakweer, Al-Hindi, Alassiri, Robinson and Abedalthagafi.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fmed.2022.947456
• Title of Journal or Parent Work: FRONTIERS IN MEDICINE
• Volume: 9
• Start Page: 947456
• End Page: 947456
• Grant/Funding Information: The funding body was not involved in any stage of the study and had no role in the design of the study, the collection, analysis, and interpretation of data or the writing of the manuscript.; This work was technically supported by the Saudi Human Genome Program at KACST (MAb).
• Keywords: PI3K; colorectal cancer; CDK; Life Sciences & Biomedicine; breast cancer; genetics diversity; brain metastasis; MAPK; BRANCHED EVOLUTION; Medicine, General & Internal; Science & Technology; General & Internal Medicine; comprehensive genomic panel
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Pathology

Abstract

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.