The landscape of primary mismatch repair deficient gliomas in children, adolescents, and young adults: a multi-cohort study

• Published in: The lancet oncology 2024-12
• Main Authors: Negm, Logine, Chung, Jiil, Nobre, Liana, Bennett, Julie, Fernandez, Nicholas R, Nunes, Nuno Miguel, Liu, Zhihui Amy, Komosa, Martin, Aronson, Melyssa, Zhang, Cindy, Stengs, Lucie, Bianchi, Vanessa, Edwards, Melissa, Doherty, Sheradan, Ercan, Ayse Bahar, Cardenas, Maria F, Macias, Michael, Lueder, Matthew R, Ku, Michelle, Johnson, Monique, Chang, Yuan, Dimayacyac, Jose Rafael, Kraya, Adam A, Guo, Yiran, Naky, Stav, Keith, Julia, Gao, Andrew F, Munoz, David G, Nguyen, Lananh, Tsang, Derek S, Lim-Fat, Mary Jane, Das, Sunit, Shlien, Adam, Ramaswamy, Vijay, Huang, Annie, Malkin, David, Villani, Anita, Ertl-Wagner, Birgit, Levine, Adrian, Robinson, Giles W, Pollock, Brad H, Spector, Logan G, Sei, Shizuko, Dirks, Peter B, Getz, Gad, Nichols, Kim E, Resnick, Adam C, Wheeler, David A, Das, Anirban, Maruvka, Yosef E, Hawkins, Cynthia, Tabori, Uri
• Format: Article
• Language: English
• ISSN: 1470-2045; 1474-5488; 1474-5488
• DOI: 10.1016/S1470-2045(24)00640-5

Gliomas are a major cause of cancer-related death among children, adolescents, and young adults (age 0–40 years). Primary mismatch repair deficiency (MMRD) is a pan-cancer mechanism with unique biology and therapeutic opportunities. We aimed to determine the extent and impact of primary MMRD in gliomas among children, adolescents, and young adults. Clinical and molecular data were collected from a population-based cohort of children, adolescents, and young adults with gliomas from Toronto (TOR-Ped, age 0–18 years, collected Jan 1, 2000, to Dec 31, 2021; and TOR-AYA, age 18–40 years, collected Jan 1, 2000, to June 30, 2019). Additional validation paediatric cohorts from St Jude Children's Research Hospital (0–18 years, 2015–21) and the Children's Brain Tumor Network (0–18 years, 1981–2021) were used. Functional genomic tools were applied with the primary aim of assessing primary MMRD prevalence among glioma subgroups and germline impact. To evaluate the effect of primary MMRD on therapy and overall survival, Kaplan–Meier estimates were used on an additional cohort of patients with primary MMRD gliomas treated with immunotherapy. 1389 gliomas were included in the study. The prevalence of primary MMRD ranged between 3·7% and 12·4% in high-grade gliomas (overall 30 of 483; 6·2%, 95% CI 4·2–8·7) and less than 1% in low-grade gliomas (four of 899; 0·4%, 0·1–1·1; p