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
Bibliographic record
Abstract
PURPOSE 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. PATIENTS AND METHODS We 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. RESULTS 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 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]). CONCLUSION 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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".