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
PURPOSEConstitutional 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 wit...
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| Format: | Article |
| Language: | English |
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American Society of Clinical Oncology
2025-04-01
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| Series: | JCO Global Oncology |
| Online Access: | https://ascopubs.org/doi/10.1200/GO-24-00247 |
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| author | Naureen Mushtaq Khurram Minhas Farrah Bashir Soha Zahid Bilal Mazhar Qureshi Gohar Javed Shahzadi Resham Anirban Das Cynthia Hawkins Uri Tabori Eric Bouffet |
| author_facet | Naureen Mushtaq Khurram Minhas Farrah Bashir Soha Zahid Bilal Mazhar Qureshi Gohar Javed Shahzadi Resham Anirban Das Cynthia Hawkins Uri Tabori Eric Bouffet |
| author_sort | Naureen Mushtaq |
| collection | DOAJ |
| description | PURPOSEConstitutional 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.PATIENTS AND METHODSWe reviewed the data of patients age <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.RESULTSForty-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 PMS2. Three had loss of PMS2 and MLH1; two had loss of MSH6, one had loss of MSH6 and MSH2, and only one patient had loss of MSH2. Consanguinity and family history of malignancy correlated with CMMRD (P = .009, P = .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–positive patients was 20% (median follow-up, 0.910 years [95 CI, 0.380 to 1.440]).CONCLUSIONWe 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. |
| format | Article |
| id | doaj-art-e15b2f548a644eac8c60bfd767264ba0 |
| institution | OA Journals |
| issn | 2687-8941 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | American Society of Clinical Oncology |
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| series | JCO Global Oncology |
| spelling | doaj-art-e15b2f548a644eac8c60bfd767264ba02025-08-20T02:08:03ZengAmerican Society of Clinical OncologyJCO Global Oncology2687-89412025-04-011110.1200/GO-24-00247Frequency and Impact of Constitutional Mismatch Repair Deficiency in Patients With High-Grade Glioma, a Retrospective Analysis of 7 Years in Pakistan: an IRRDC StudyNaureen Mushtaq0Khurram Minhas1Farrah Bashir2Soha Zahid3Bilal Mazhar Qureshi4Gohar Javed5Shahzadi Resham6Anirban Das7Cynthia Hawkins8Uri Tabori9Eric Bouffet10Department of Oncology, Aga Khan University Hospital, Karachi, PakistanDepartment of Pathology and Laboratory Medicine, Aga Khan University Hospital Karachi, Karachi, PakistanDepartment of Oncology, Aga Khan University Hospital, Karachi, PakistanDepartment of Oncology, Aga Khan University Hospital, Karachi, PakistanDepartment of Oncology, Aga Khan University Hospital, Karachi, PakistanDepartment of Surgery, Aga Khan University Hospital, Karachi, PakistanDepartment of Oncology, Aga Khan University Hospital, Karachi, PakistanThe Hospital for Sick Children, Toronto, CanadaThe Hospital for Sick Children, Toronto, CanadaThe Hospital for Sick Children, Toronto, CanadaDepartment of Oncology, Aga Khan University Hospital, Karachi, PakistanPURPOSEConstitutional 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.PATIENTS AND METHODSWe reviewed the data of patients age <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.RESULTSForty-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 PMS2. Three had loss of PMS2 and MLH1; two had loss of MSH6, one had loss of MSH6 and MSH2, and only one patient had loss of MSH2. Consanguinity and family history of malignancy correlated with CMMRD (P = .009, P = .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–positive patients was 20% (median follow-up, 0.910 years [95 CI, 0.380 to 1.440]).CONCLUSIONWe 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.https://ascopubs.org/doi/10.1200/GO-24-00247 |
| spellingShingle | Naureen Mushtaq Khurram Minhas Farrah Bashir Soha Zahid Bilal Mazhar Qureshi Gohar Javed Shahzadi Resham Anirban Das Cynthia Hawkins Uri Tabori Eric Bouffet 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 JCO Global Oncology |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://ascopubs.org/doi/10.1200/GO-24-00247 |
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