{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:32:37Z","timestamp":1787020357052,"version":"build-2736575974"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Medizinische Fakult\u00e4t Heidelberg der Universit\u00e4t Heidelberg"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mismatch repair deficiency (MMRD) contributes substantially to early-onset colorectal carcinoma (CRC) and pediatric malignancies in Jordan. Approximately 19% of CRCs diagnosed in adults younger than 45 years exhibit MMRD by immunohistochemistry (IHC). In pediatric tumors, MMRD accounts for 39% of high-grade gliomas (HGGs) and 44% of CRCs, likely reflecting the increased prevalence of constitutional MMRD (CMMRD) in this highly consanguineous population. However, the molecular characterization of MMRD-associated tumors in the Middle East remains limited. We analyzed 14 Jordanian patients (&lt;\u200945 years) from 12 families with clinical or IHC evidence of MMRD, including four HGGs and 11 CRCs; five patients were children. Pathogenic or likely pathogenic\n                    <jats:italic>MMR<\/jats:italic>\n                    variants were identified in nine families, including one sibling pair, comprising five frameshift indels, three single nucleotide variants, and one large deletion. A variant of uncertain significance in\n                    <jats:italic>MSH6<\/jats:italic>\n                    was identified in another sibling pair. Apparent large deletions suggestive of sequencing artifacts in six patients highlighted the need for confirmatory copy number analysis by multiplex ligation-dependent probe amplification. Tumor mutational burden ranged from 2 to 352 variants\/Mb (median, 23). Microsatellite instability was low in seven tumors, likely reflecting degraded DNA from older formalin-fixed paraffin-embedded samples. Mutational signatures were concordant with the molecular findings in most cases. Notably, the only ultrahypermutated tumor harbored a canonical somatic\n                    <jats:italic>POLE<\/jats:italic>\n                    p.(Val411Leu) proofreading-domain mutation together with polymerase-associated mutational signatures, consistent with combined MMRD and polymerase proofreading deficiency. This study represents the first comprehensive molecular characterization of MMRD-associated tumors in Jordan.\n                  <\/jats:p>","DOI":"10.1007\/s12672-026-05717-3","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:46:27Z","timestamp":1786988787000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular characterization of mismatch repair deficient tumors in young Jordanian patients"],"prefix":"10.1007","volume":"17","author":[{"given":"Olfat","family":"Ahmad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iyad","family":"Sultan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maysa","family":"Hussaini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama","family":"Alsmadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Sutter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Hirsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Autry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Previti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asta","family":"F\u00f6rsti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Schwalm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lama","family":"AbuJamous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisreen","family":"Amayiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayada Abu","family":"Shanap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rola","family":"Amareen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salsabeel","family":"Aljawabrah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Fryjat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Al-Naimat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Areen","family":"Qaisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala","family":"Alnaimat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Reuss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas R.","family":"Fernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anirban","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uri","family":"Tabori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan M.","family":"Pfister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian P.","family":"Schaaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"issue":"3","key":"5717_CR1","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nrc3878","volume":"15","author":"HT Lynch","year":"2015","unstructured":"Lynch HT, Snyder CL, Shaw TG, Heinen CD, Hitchins MP. 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The study was approved by the Institutional Review Board of KHCC (ethics approval number: 140\u00a0F-2021) and was conducted in accordance with the ethical standards of the institutional research committee and the principles of the Declaration of Helsinki. Freely given, informed consent to participate in the study and to publish the results was obtained from all participants prior to inclusion. For participants under the age of 16, informed consent was obtained from a parent or legal guardian. Written informed consent for publication of pseudonymized clinical and molecular data was obtained from all participants or their legal guardians, where applicable. Participants were informed about the purpose of the study and the intended publication of their data in a scientific journal.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"As indicated in the ethics statement, informed consent was obtained from participants and\/or their parents including consent to participate and to publish their results.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"1198"}}