Mismatch Repair Deficiency and Lynch Syndrome Among Adult Patients With Glioma
2023; Lippincott Williams & Wilkins; Issue: 7 Linguagem: Inglês
10.1200/po.22.00525
ISSN2473-4284
AutoresPatrick R. Benusiglio, Fikret Elder, Mehdi Touat, Alexandre Perrier, Marc Sanson, Chrystelle Colas, Léa Guerrini‐Rousseau, Duy Thanh Tran, Nesrine Trabelsi, Alain Carpentier, Yannick Marie, Clovis Adam, Michèle Bernier, Dominique Cazals–Hatem, Karima Mokhtari, Suzanne Tran, Bertrand Mathon, Laurent Capelle, Marion Dhooge, Ahmed Idbaïh, Agustí Alentorn, Caroline Houillier, Caroline Dehais, Khê Hoang‐Xuan, Stefania Cuzzubbo, Alain Carpentier, Alex Duval, Florence Coulet, Franck Bielle,
Tópico(s)Cancer Genomics and Diagnostics
ResumoPURPOSE The Lynch syndrome (LS)-glioma association is poorly documented. As for mismatch repair deficiency (MMRd) in glioma, a hallmark of LS-associated tumors, there are only limited data available. We determined MMRd and LS prevalence in a large series of unselected gliomas, and explored the associated characteristics. Both have major implications in terms of treatment, screening, and prevention. METHODS Somatic next-generation sequencing was performed on 1,225 treatment-naive adult gliomas referred between 2017 and June 2022. For gliomas with ≥1 MMR pathogenic variant (PV), MMR immunohistochemistry (IHC) was done. Gliomas with ≥1 PV and protein expression loss were considered MMRd. Eligible patients had germline testing. To further explore MMRd specifically in glioblastomas, isocitrate dehydrogenase (IDH)-wild type (wt), we performed IHC, and complementary sequencing when indicated, in a series of tumors diagnosed over the 2007-2021 period. RESULTS Nine gliomas were MMRd (9/1,225; 0.73%). Age at glioma diagnosis was <50 years for all but one case. Eight were glioblastomas, IDH-wt, and one was an astrocytoma, IDH-mutant. ATRX (n = 5) and TP53 (n = 8) PV were common. There was no TERT promoter PV or EGFR amplification. LS prevalence was 5/1,225 (0.41%). One 77-year-old patient was a known LS case. Four cases had a novel LS diagnosis, with germline PV in MSH2 (n = 3) and MLH1 (n = 1). One additional patient had PMS2-associated constitutional mismatch repair deficiency. Germline testing was negative in three MSH6-deficient tumors. In the second series of glioblastomas, IDH-wt, MMRd prevalence was 12.5% in the <40-year age group, 2.6% in the 40-49 year age group, and 1.6% the ≥50 year age group. CONCLUSION Screening for MMRd and LS should be systematic in glioblastomas, IDH-wt, diagnosed under age 50 years.
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