{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T17:17:06Z","timestamp":1782407826015,"version":"3.54.5"},"reference-count":32,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"11","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Glob Oncol"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>Constitutional mismatch repair deficiency (CMMRD) is a genetic cancer predisposition syndrome among children and young adults. This study aimed to evaluate the frequency of CMMRD among patients with pediatric high-grade glioma (pHGG) in a single tertiary care center in Pakistan, a country with high consanguinity rates.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>PATIENTS AND METHODS<\/jats:title>\n            <jats:p>We reviewed the data of patients age &lt;18 years with pHGG, anaplastic astrocytoma, and diffuse midline glioma (DMG) with CMMRD testing between 2016 and 2023. CMMRD testing was done using the Aronson et al criteria. A few patients were sent to Sick Kids, Toronto, to review the mismatch repair protein stains via multigene panels.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              Forty-seven patients were identified, with a median age of 11 years (IQR, 8-16). Headache (89.4%) was the most common symptom. Thirty-seven patients had hemispheric tumors; 12.8% and 8.5% had posterior fossa and midline tumors, respectively. Histopathology revealed 70.2% glioblastoma, 23.4% anaplastic astrocytoma, and 6.4% DMG. CMMRD was positive in 15 of 47 patients (31.9%). Eight patients had loss of\n              <jats:italic>PMS2<\/jats:italic>\n              . Three had loss of\n              <jats:italic>PMS2<\/jats:italic>\n              and\n              <jats:italic>MLH1<\/jats:italic>\n              ; two had loss of\n              <jats:italic>MSH6<\/jats:italic>\n              , one had loss of\n              <jats:italic>MSH6<\/jats:italic>\n              and\n              <jats:italic>MSH2<\/jats:italic>\n              , and only one patient had loss of\n              <jats:italic>MSH2<\/jats:italic>\n              . Consanguinity and family history of malignancy correlated with CMMRD (\n              <jats:italic>P<\/jats:italic>\n              = .009,\n              <jats:italic>P<\/jats:italic>\n              = .031, respectively). Two-year overall survival of all patients was 23.4% (median follow-up, 0.59 years [95% CI, 0.000 to 1.171]). Two-year overall survival of mismatch repair deficiency\u2013positive patients was 20% (median follow-up, 0.910 years [95 CI, 0.380 to 1.440]).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>We found a high frequency of CMMRD among patients with pHGG, particularly with positive consanguinity. Our study highlights the significance of genetic testing and surveillance. It is essential to develop low and middle income country-tailored protocols due to limited access and financial constraints associated with using immune checkpoint inhibitors.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/go-24-00247","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T20:59:16Z","timestamp":1737061156000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Frequency and Impact of Constitutional Mismatch Repair Deficiency in Patients With High-Grade Glioma, a Retrospective Analysis of 7 Years in Pakistan: an IRRDC Study"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5461-3350","authenticated-orcid":true,"given":"Naureen","family":"Mushtaq","sequence":"first","affiliation":[{"name":"Department of Oncology, Aga Khan University Hospital, Karachi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6210-4636","authenticated-orcid":true,"given":"Khurram","family":"Minhas","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Aga Khan University Hospital Karachi, Karachi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2460-9388","authenticated-orcid":true,"given":"Farrah","family":"Bashir","sequence":"additional","affiliation":[{"name":"Department of Oncology, Aga Khan University Hospital, Karachi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8195-4265","authenticated-orcid":true,"given":"Soha","family":"Zahid","sequence":"additional","affiliation":[{"name":"Department of Oncology, Aga Khan University Hospital, Karachi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0138-7628","authenticated-orcid":true,"given":"Bilal Mazhar","family":"Qureshi","sequence":"additional","affiliation":[{"name":"Department of Oncology, Aga Khan University Hospital, Karachi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gohar","family":"Javed","sequence":"additional","affiliation":[{"name":"Department of Surgery, Aga Khan University Hospital, Karachi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3969-7381","authenticated-orcid":true,"given":"Shahzadi","family":"Resham","sequence":"additional","affiliation":[{"name":"Department of Oncology, Aga Khan University Hospital, Karachi, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7653-9529","authenticated-orcid":true,"given":"Anirban","family":"Das","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2618-4402","authenticated-orcid":true,"given":"Cynthia","family":"Hawkins","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5019-2683","authenticated-orcid":true,"given":"Uri","family":"Tabori","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6832-6539","authenticated-orcid":true,"given":"Eric","family":"Bouffet","sequence":"additional","affiliation":[{"name":"Department of Oncology, Aga Khan University Hospital, Karachi, Pakistan"},{"name":"The Hospital for Sick Children, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_6_2_2","first-page":"102263","article-title":"Primary cervical glioblastoma multiforme as a presentation of constitutional mismatch repair deficiency: Case report and literature review","volume":"64","author":"Jarrar SM","year":"2021","unstructured":"Jarrar SM, Daoud SS, Jbarah OF, et al: Primary cervical glioblastoma multiforme as a presentation of constitutional mismatch repair deficiency: Case report and literature review. Ann Med Surg (Lond) 64:102263, 2021","journal-title":"Ann Med Surg (Lond)"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-022-01403-9"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102284"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.12669\/pjms.39.5.6300"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094629"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29724"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.3340\/jkns.2018.0031"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-020-04986-9"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2020.561487"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.28309"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12905-022-01704-2"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2020-107627"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.26.8169"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nou349"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0021932098002612"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02873"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-0574"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-102238"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.26249"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-3105"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16723"},{"key":"e_1_3_6_23_2","first-page":"vdz033","article-title":"Constitutional mismatch repair deficiency-associated brain tumors: Report from the European C4CMMRD consortium","volume":"1","author":"Guerrini-Rousseau L","year":"2019","unstructured":"Guerrini-Rousseau L, Varlet P, Colas C, et al: Constitutional mismatch repair deficiency-associated brain tumors: Report from the European C4CMMRD consortium. Neurooncol Adv 1:vdz033, 2019","journal-title":"Neurooncol Adv"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-1151"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noq191"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/now038"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.66.6552"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01581-6"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.06.018"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(24)00026-3"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","unstructured":"Patel A Hande V MR K et al: Effectiveness of immune checkpoint inhibitors in various tumor types treated by low per-weight and conventional doses at a tertiary care center in Mumbai. JCO Glob Oncol 10.1200\/GO.23.00312","DOI":"10.1200\/GO.23.00312"},{"key":"e_1_3_6_32_2","volume-title":"Global Platform for Access to Childhood Cancer Medicines | St. Jude Global Alliance","unstructured":"Global Platform for Access to Childhood Cancer Medicines | St. Jude Global Alliance. https:\/\/global.stjude.org\/en-us\/featured\/global-platform-for-access-to-childhood-cancer-medicines.html"},{"key":"e_1_3_6_33_2","volume-title":"About the ATOM Coalition | UICC","unstructured":"About the ATOM Coalition | UICC. https:\/\/www.uicc.org\/atom\/about-atom-coalition"}],"container-title":["JCO Global Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/GO-24-00247","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T20:59:36Z","timestamp":1737061176000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/GO-24-00247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":32,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1200\/GO-24-00247"],"URL":"https:\/\/doi.org\/10.1200\/go-24-00247","relation":{},"ISSN":["2687-8941"],"issn-type":[{"value":"2687-8941","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2024-06-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-14","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2400247"}}