BIOM-01. CMMRD-Associated Brain Tumors: A Molecular Analysis from a Tertiary Care Center in a Lower Middle-Income Country

Abstract Background Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessive condition that arises from inherited mutations in the mismatch repair (MMR) genes. These genes are responsible for repairing mistakes that occur during DNA replication. Mutations in these genes can cause a buildup of errors increasing the risk of various types of cancers, particularly in the brain and digestive system. Objective In this case series, we aimed to describe the molecular characteristics of CMMRD-associated brain tumors in patients from our center. Methods Consecutive sampling was used to identify all cases reported in our Section between January 1, 2020, and June 30, 2023. A retrospective review of patient data was conducted to retrieve cases, and diagnoses were confirmed. Patients were prospectively followed up via telephone calls after 12 months. Ethical exemption was obtained as only de-identified data was utilized in the study. Results Fourteen patients with CMMRD-associated brain tumors were diagnosed and treated at our tertiary care center. Microsatellite instability (MSI) and DNA mismatch repair (MMR) protein expression were evaluated using immunohistochemistry. All 14 patients had biallelic pathogenic germline variants in one of the four MMR genes. Thirteen patients had glioblastoma (WHO grade IV), and one had a low-grade glioma (WHO grade 1). MSI-high status was identified in all cases. Reduced or absent expression of one or more MMR proteins was observed in all cases, with PMS2 deficiency being the most common abnormality. Conclusion Our study highlights the importance of MSI and MMR protein expression analysis in the diagnosis and management of CMMRD-associated brain tumors. Our findings contribute to a better understanding of the molecular characteristics of CMMRD-associated brain tumors in our patient population and may inform the development of more effective surveillance and treatment strategies for these patients.