{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T16:01:15Z","timestamp":1766073675647,"version":"3.48.0"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UCLA SPORE in Brain Cancer","award":["P50CA211015"],"award-info":[{"award-number":["P50CA211015"]}]},{"name":"UCLA SPORE in Brain Cancer","award":["DOD W81XWH-18-1-0496"],"award-info":[{"award-number":["DOD W81XWH-18-1-0496"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>RECQL4 plays an important role in maintaining the integrity of the genome and regulating DNA replication. However, the role of RECQL4 in CNS tumors remains unknown. Sequencing data were reviewed and immunohistochemistry was performed on a variety of glial and nerve sheath tumors. Functional studies were performed in glioma (U251) and malignant peripheral nerve sheath tumors (MPNSTs) (NF90-8, ST88-14) cell lines following RECQL4 knockdown and treatment with ATR-inhibitors. Across 1580 CNS tumors, RECQL4 gene variants were identified in 71 cases (4.5%), with 21 (29.6%) of probable pathogenic significance. RECQL4 expression differed significantly across glioma subgroups (P\u2009=\u20090.012). Low-grade gliomas (diffuse: median H-score 57.5; circumscribed: median 130) showed lower expression than high-grade gliomas (median 145, P\u2009&amp;lt;\u20090.05). Neurofibromas displayed higher RECQL4 expression (median 160) compared with MPNSTs (median 97.5, P\u2009&amp;lt;\u20090.001). Among MPNSTs, NF1-associated cases (n\u2009=\u200924, median 95) expressed significantly less RECQL4 than sporadic cases (n\u2009=\u20098, median 162.5, P\u2009&amp;lt;\u20090.001). RECQL4 knockdown in glioma and MPNST cell lines resulted in increased apoptosis and susceptibility to ATR-inhibitors. Our findings show that RECQL4 expression has divergent patterns across tumor types and that targeting RECQL4 may dampen tumor survival and enhance susceptibility to ATR inhibitor therapy in CNS tumors.<\/jats:p>","DOI":"10.1093\/jnen\/nlaf129","type":"journal-article","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T11:59:21Z","timestamp":1761393561000},"page":"1191-1201","source":"Crossref","is-referenced-by-count":0,"title":["<i>RECQL4<\/i>\n                    alterations in gliomas and nerve sheath tumors: Expression patterns and therapeutic implications"],"prefix":"10.1093","volume":"84","author":[{"given":"Sarra","family":"Belakhoua","sequence":"first","affiliation":[{"name":"Department of Pathology, New York University , New York City, NY,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California , Los Angeles, CA,","place":["United States"]},{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda\u2014Ospedale Maggiore Policlinico , Milan,","place":["Italy"]},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan , Milan,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swati","family":"Dubey","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California , Los Angeles, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simran","family":"Rai","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California , Los Angeles, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liam","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Minnesota , Minneapolis, MN,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University , Baltimore, MD,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aparna","family":"Pallavajjala","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University , Baltimore, MD,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University , Baltimore, MD,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melike","family":"Pekmezci","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California, San Francisco , San Francisco, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Stojanova","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston Medical Center , Boston, MA,","place":["United States"]},{"name":"Boston University Chobanian & Avedisian School of Medicine , Boston, MA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M","family":"Heaphy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston Medical Center , Boston, MA,","place":["United States"]},{"name":"Boston University Chobanian & Avedisian School of Medicine , Boston, MA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles G","family":"Eberhart","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University , Baltimore, MD,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8662-1219","authenticated-orcid":false,"given":"Fausto J","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University , New York City, NY,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"2025121810571393700_nlaf129-B1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1097\/01.gim.0000214457.58378.1a","article-title":"The versatile RECQL4","volume":"8","author":"Kellermayer","year":"2006","journal-title":"Genet Med"},{"key":"2025121810571393700_nlaf129-B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2017.10.021","article-title":"Human RecQL4 helicase plays multifaceted roles in the genomic stability of normal and cancer cells","volume":"413","author":"Mo","year":"2018","journal-title":"Cancer Lett"},{"key":"2025121810571393700_nlaf129-B3","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1074\/jbc.M111.295063","article-title":"RECQL4, the protein mutated in Rothmund-Thomson syndrome, functions in telomere maintenance","volume":"287","author":"Ghosh","year":"2012","journal-title":"J Biol Chem"},{"key":"2025121810571393700_nlaf129-B4","first-page":"15","article-title":"RecQ helicases in DNA double strand break repair and telomere maintenance","volume":"736","author":"Singh","year":"2012","journal-title":"Mutat Res"},{"key":"2025121810571393700_nlaf129-B5","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.canlet.2005.07.042","article-title":"Rothmund-Thomson syndrome and RECQL4 defect: splitting and lumping","volume":"232","author":"Larizza","year":"2006","journal-title":"Cancer 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