{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:18:49Z","timestamp":1790759929126,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002738","name":"Assistance Publique - H\u00f4pitaux de Paris","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012946","name":"Association Sorbonne Universit\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012946","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Mesial Temporal Lobe Epilepsy\u2010associated Hippocampal Sclerosis (MTLE\u2010HS) is a syndrome associated with various aetiologies. We previously identified CD34\u2010positive extravascular stellate cells (CD34+ cells) possibly related to\n                      <jats:italic>BRAF<\/jats:italic>\n                      <jats:sup>V600E<\/jats:sup>\n                      oncogenic variant in a subset of MTLE\u2010HS. We aimed to identify the\n                      <jats:italic>BRAF<\/jats:italic>\n                      <jats:sup>V600E<\/jats:sup>\n                      oncogenic variants and characterise the CD34+ cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analysed\n                      <jats:italic>BRAF<\/jats:italic>\n                      <jats:sup>V600E<\/jats:sup>\n                      oncogenic variant by digital droplet Polymerase Chain Reaction in 53 MTLE\u2010HS samples (25 with CD34+ cells) and nine non\u2010expansive neocortical lesions resected during epilepsy surgery (five with CD34+ cells). Ex vivo multi\u2010electrode array recording, immunolabelling, methylation microarray and single nuclei RNAseq were performed on\n                      <jats:italic>BRAF<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>wildtype<\/jats:italic>\n                      <\/jats:sup>\n                      MTLE\u2010HS and\n                      <jats:italic>BRAF<\/jats:italic>\n                      <jats:sup>V600E<\/jats:sup>\n                      mutant non\u2010expansive lesion of hippocampus and\/or neocortex.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a\n                      <jats:italic>BRAF<\/jats:italic>\n                      <jats:sup>V600E<\/jats:sup>\n                      oncogenic variant in five MTLE\u2010HS samples with CD34+ cells (19%) and in five neocortical samples with CD34+ cells (100%). Single nuclei RNAseq of resected samples revealed two unique clusters of abnormal cells (including CD34+ cells) associated with senescence and oligodendrocyte development in both hippocampal and neocortical\n                      <jats:italic>BRAF<\/jats:italic>\n                      <jats:sup>V600E<\/jats:sup>\n                      mutant samples. The co\u2010expression of the oncogene\u2010induced senescence marker p16\n                      <jats:sup>INK4A<\/jats:sup>\n                      and the outer subventricular zone radial glia progenitor marker HOPX in CD34+ cells was confirmed by multiplex immunostaining. Pseudotime analysis showed that abnormal cells share a common lineage from progenitors to myelinating oligodendrocytes. Epilepsy surgery led to seizure freedom in eight of the 10 patients with\n                      <jats:italic>BRAF<\/jats:italic>\n                      mutant lesions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      <jats:italic>BRAF<\/jats:italic>\n                      <jats:sup>V600E<\/jats:sup>\n                      underlies a subset of MTLE\u2010HS and epileptogenic non\u2010expansive neocortical focal lesions. Detection of the oncogenic variant may help diagnosis and open perspectives for targeted therapies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12937","type":"journal-article","created":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T05:10:28Z","timestamp":1695445828000},"page":"1-865","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hippocampal and neocortical\n                    <i>BRAF<\/i>\n                    mutant non\u2010expansive lesions in focal epilepsies"],"prefix":"10.1111","volume":"49","author":[{"given":"Julie","family":"Lerond","sequence":"first","affiliation":[{"name":"Institut du Cerveau\u2013Paris Brain Institute\u2013ICM, Inserm, CNRS Sorbonne Universit\u00e9  Paris 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