{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T17:56:14Z","timestamp":1768413374088,"version":"3.49.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fmed.2022.947456","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T22:02:24Z","timestamp":1669327344000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinicopathologic and genomic characterizations of brain metastases using a comprehensive genomic panel"],"prefix":"10.3389","volume":"9","author":[{"given":"Duna H.","family":"Barakeh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebtehal","family":"Alsolme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatimah","family":"Alqubaishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amal","family":"Almutairi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lamees","family":"Alhabeeb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally","family":"Al Abdulmohsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahd S.","family":"Almohsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doaa","family":"Alayed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara Rashid","family":"AlAnazi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malak","family":"AlZahrani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albandari Mohammed","family":"Binowayn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah S.","family":"AlOtaibi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fahad A.","family":"Alkhureeb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wafa","family":"Al Shakweer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hindi","family":"Al-Hindi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Alassiri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather A.","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malak","family":"Abedalthagafi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"3475","DOI":"10.1200\/JCO.2015.60.9503","article-title":"Treatment of brain metastases.","volume":"33","author":"Lin","year":"2015","journal-title":"J Clin Oncol."},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.3390\/cancers14041096","article-title":"Salvage treatment for progressive brain metastases in breast cancer.","volume":"14","author":"Spa\u0142ek","year":"2022","journal-title":"Cancers."},{"key":"B3","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1093\/neuonc\/now241","article-title":"Diagnosis and treatment of brain metastases from solid tumors: guidelines from the European association of neuro-oncology (EANO).","volume":"19","author":"Soffietti","year":"2017","journal-title":"Neuro Oncol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"108","DOI":"10.2174\/1574892815666201127114224","article-title":"Next generation sequencing in the management of leptomeningeal metastases of non-small cell lung cancer: a case report and literature review.","volume":"16","author":"Li","year":"2021","journal-title":"Recent Pat Anticancer Drug Discov."},{"key":"B5","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/s41586-020-2969-2","article-title":"A metastasis map of human cancer cell lines.","volume":"588","author":"Jin","year":"2020","journal-title":"Nature."},{"key":"B6","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21124463","article-title":"Extracellular vesicles in cancer metastasis: potential as therapeutic targets and materials.","volume":"21","author":"Kogure","year":"2020","journal-title":"Int J Mol Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.3892\/mco.2015.623","article-title":"Reasons for cancer metastasis: a holistic perspective.","volume":"3","author":"Wang","year":"2015","journal-title":"Mol Clin Oncol."},{"key":"B8","doi-asserted-by":"crossref","first-page":"5534","DOI":"10.1002\/cam4.1697","article-title":"Clinical landscape of cancer metastases.","volume":"7","author":"Riihim\u00e4ki","year":"2018","journal-title":"Cancer Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"3662","DOI":"10.1002\/cam4.1661","article-title":"Frequency and clinicopathological features of metastasis to liver, lung, bone, and brain from gastric cancer: a SEER-based study.","volume":"7","author":"Qiu","year":"2018","journal-title":"Cancer Med."},{"key":"B10","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.3390\/ijms14011383","article-title":"Role of the blood-brain barrier in the formation of brain metastases.","volume":"14","author":"Wilhelm","year":"2013","journal-title":"Int J Mol Sci."},{"key":"B11","first-page":"295","article-title":"Brain metastases.","volume":"18","author":"Lu-Emerson","year":"2012","journal-title":"Continuum."},{"key":"B12","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJMoa1113205","article-title":"Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.","volume":"366","author":"Gerlinger","year":"2012","journal-title":"N Engl J Med."},{"key":"B13","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nm.1944","article-title":"Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer.","volume":"15","author":"Liu","year":"2009","journal-title":"Nat Med."},{"key":"B14","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s10555-016-9649-6","article-title":"The role of HER2, EGFR, and other receptor tyrosine kinases in breast cancer.","volume":"35","author":"Hsu","year":"2016","journal-title":"Cancer Metastasis Rev."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1158\/2159-8290.CD-15-0369","article-title":"Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets.","volume":"5","author":"Brastianos","year":"2015","journal-title":"Cancer Discov."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2017.00230","article-title":"Genetic characterization of brain metastases in the era of targeted therapy.","volume":"7","author":"Han","year":"2017","journal-title":"Front Oncol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e123","DOI":"10.1200\/EDBK_100006","article-title":"Targeted therapy in brain metastases: ready for primetime?","volume":"35","author":"Venur","year":"2016","journal-title":"Am Soc Clin Oncol Educ Book."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0228356","article-title":"Clinical management and genomic profiling of pediatric low-grade gliomas in Saudi Arabia.","volume":"15","author":"Mobark","year":"2020","journal-title":"PLoS One."},{"key":"B19","doi-asserted-by":"publisher","first-page":"686","DOI":"10.18632\/oncotarget.27909","article-title":"Landscape of somatic mutations in breast cancer: new opportunities for targeted therapies in Saudi Arabian patients.","volume":"12","author":"Barakeh","year":"2021","journal-title":"Oncotarget."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2438","DOI":"10.1002\/glia.23485","article-title":"PI3K: a master regulator of brain metastasis-promoting macrophages\/microglia.","volume":"66","author":"Blazquez","year":"2018","journal-title":"Glia."},{"key":"B21","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1093\/neuonc\/noab159","article-title":"The PI3K\/Akt\/mTOR pathway as a preventive target in melanoma brain metastasis.","volume":"24","author":"Tehranian","year":"2022","journal-title":"Neuro Oncol."},{"key":"B22","first-page":"342","article-title":"PI3K\/Akt\/mTOR inhibitors in breast cancer.","volume":"12","author":"Lee","year":"2015","journal-title":"Cancer Biol Med."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2014.00064","article-title":"Targeting PI3K\/Akt\/mTOR signaling in cancer.","volume":"4","author":"Porta","year":"2014","journal-title":"Front Oncol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"6317","DOI":"10.18632\/oncotarget.27238","article-title":"Central nervous system-specific efficacy of CDK4\/6 inhibitors in randomized controlled trials for metastatic breast cancer.","volume":"10","author":"Nguyen","year":"2019","journal-title":"Oncotarget."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1111\/cas.13957","article-title":"Preclinical characterization of SHR6390, a novel CDK 4\/6 inhibitor, in vitro and in human tumor xenograft models.","volume":"110","author":"Long","year":"2019","journal-title":"Cancer Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/s43018-021-00198-5","article-title":"Palbociclib demonstrates intracranial activity in progressive brain metastases harboring cyclin-dependent kinase pathway alterations.","volume":"2","author":"Brastianos","year":"2021","journal-title":"Nat Cancer."},{"key":"B27","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1007\/s11060-019-03260-6","article-title":"CDK 4\/6 inhibitors and stereotactic radiation in the management of hormone receptor positive breast cancer brain metastases.","volume":"144","author":"Figura","year":"2019","journal-title":"J Neurooncol."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0474-4","article-title":"Inhibition of cyclin-dependent kinase 4 as a potential therapeutic strategy for treatment of synovial sarcoma.","volume":"9","author":"Li","year":"2018","journal-title":"Cell Death Dis."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/9525207","article-title":"Inhibition of the CDK4\/6-cyclin D-Rb pathway by ribociclib augments chemotherapy and immunotherapy in renal cell carcinoma.","volume":"2020","author":"Chen","year":"2020","journal-title":"BioMed Res Int."},{"key":"B30","doi-asserted-by":"crossref","DOI":"10.3390\/cancers11101618","article-title":"A comprehensive review on MAPK: a promising therapeutic target in cancer.","volume":"11","author":"Braicu","year":"2019","journal-title":"Cancers."},{"key":"B31","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1002\/cncr.28864","article-title":"The MAPK pathway across different malignancies: a new perspective.","volume":"120","author":"Burotto","year":"2014","journal-title":"Cancer."},{"key":"B32","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1002\/cbin.11187","article-title":"Extracellular-signal-regulated kinase\/mitogen-activated protein kinase signaling as a target for cancer therapy: an updated review.","volume":"43","author":"Najafi","year":"2019","journal-title":"Cell Biol Int."},{"key":"B33","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21082893","article-title":"MAP kinases pathways in gastric cancer.","volume":"21","author":"Magnelli","year":"2020","journal-title":"Int J Mol Sci."},{"key":"B34","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.acuro.2011.07.013","article-title":"[Role of mitogen-activated protein kinase (MAPK) in the sporadic renal cell carcinoma].","volume":"36","author":"Salinas-S\u00e1nchez","year":"2012","journal-title":"Actas Urol Esp."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13122888","article-title":"Leptomeningeal metastases from solid tumors: recent advances in diagnosis and molecular approaches.","volume":"13","author":"Pellerino","year":"2021","journal-title":"Cancers."},{"key":"B36","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1042\/BCJ20210084","article-title":"The roles of epigenetics in cancer progression and metastasis.","volume":"478","author":"Chen","year":"2021","journal-title":"Biochem J."},{"key":"B37","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.molonc.2016.09.008","article-title":"Epigenetic determinants of metastasis.","volume":"11","author":"Patel","year":"2017","journal-title":"Mol Oncol."},{"key":"B38","first-page":"7025","article-title":"Novel somatic mutations of the MET oncogene in human carcinoma metastases activating cell motility and invasion.","volume":"62","author":"Lorenzato","year":"2002","journal-title":"Cancer Res."},{"key":"B39","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41416-020-01127-6","article-title":"Genomic control of metastasis.","volume":"124","author":"Patel","year":"2021","journal-title":"Br J Cancer."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-020-07172-x","article-title":"Detection of genes mutations in cerebrospinal fluid circulating tumor DNA from neoplastic meningitis patients using next generation sequencing.","volume":"20","author":"Zhao","year":"2020","journal-title":"BMC Cancer."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0228356","article-title":"LGG-01. Clinical management and genomic profiling of pediatric low-grade gliomas in Saudi Arabia.","volume":"22","author":"Mobark","year":"2020","journal-title":"Neuro Oncol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.947456\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T22:02:37Z","timestamp":1669327357000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.947456\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,24]]},"references-count":41,"alternative-id":["10.3389\/fmed.2022.947456"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.947456","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,24]]},"article-number":"947456"}}