Mismatch Repair Deficiency and Lynch Syndrome Among Adult Patients With Glioma

• DOI: 10.1200/po.22.00525
• Publication Date: 2023-06-01T20:01:00Z
• Authors: Patrick R. Benusi...; Fikret Elder; Mehdi Touat; Alexandre Perrier; Marc Sanson; Chrystelle Colas; Lea Guerrini-Rous...; Duy Thanh Tran; Nesrine Trabelsi; Catherine Carpentier; Yannick Marie; Clovis Adam; Michèle Bernier; Dominique Cazals-...; Karima Mokhtari; Suzanne Tran; Bertrand Mathon; Laurent Capelle; Marion Dhooge; Ahmed Idbaih; Agusti Alentorn; Caroline Houillier; Caroline Dehais; Khe Hoang-Xuan; Stefania Cuzzubbo; Antoine Carpentier; Alex Duval; Florence Coulet; Franck Bielle
• Keywords: Lynch Syndrome

PURPOSE 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 large series unselected gliomas, explored the associated characteristics. Both have major implications terms treatment, screening, prevention. METHODS Somatic next-generation sequencing was performed on 1,225 treatment-naive adult gliomas referred between 2017 June 2022. For with ≥1 MMR pathogenic variant (PV), immunohistochemistry (IHC) done. Gliomas PV protein expression loss were considered MMRd. Eligible patients had germline testing. To further explore specifically glioblastomas, isocitrate dehydrogenase (IDH)-wild type (wt), we IHC, complementary when indicated, tumors diagnosed over 2007-2021 period. RESULTS Nine (9/1,225; 0.73%). Age at glioma diagnosis <50 years all but one case. Eight IDH-wt, an astrocytoma, IDH-mutant. ATRX (n = 5) TP53 8) common. There no TERT promoter or EGFR amplification. 5/1,225 (0.41%). One 77-year-old patient known Four cases novel diagnosis, MSH2 3) MLH1 1). additional PMS2-associated constitutional deficiency. Germline testing negative three MSH6-deficient tumors. In second 12.5% <40-year age group, 2.6% 40-49 year 1.6% ≥50 group. CONCLUSION Screening should be systematic under 50 years.