Article
Induction of a mismatch repair deficient genotype by tailored chemical mutagenesis in experimental models of cancer.
Cancer cell - 14 Jul 2025
Rousseau Benoit, Patel Mitesh, Artz Oliver, Vlachos Georgios, Patel Shrey, Hayatt Omar, Argilés Guillem, Foote Michael B, Luo Lingqi, Shah Rachna, Mehta Shub, Rangavajhula Karthik, Stewart Caitlin M, Gerber Drew, Bhattacharya Rohini, Stephens Dennis, Mieles David, Randrian Violaine, Abdelfattah Somer, Zhang Lin, Membreno-Berganza Nathalie, Lamendola-Essel Michelle F, Piastra-Facon Florence, Vidal Joana, Johannet Paul, Lu Steve, White James R, Maron Steven B, Barlas Afsar, Weipert Caroline M, Rosiek Eric, Zhang Taotao, He Bing, Monette Sebastien, Qu Rui, Fidele Deborah, Bowker Sydney, Kahn Alec, Vitiello Pietro Paolo, Germano Giovanni, Bardelli Alberto, Mandal Rajarsi, Ma Xiaoxiao, Chan Tim A, Lu Sydney, Cercek Andrea, Abdel-Wahab Omar, de Stanchina Elisa, Segal Neil H, Diaz Luis A
Abstract excerpt
Mismatch repair deficient (MMRd) tumors harbor thousands of somatic mutations enriched for insertion-deletion (indels) conferring high sensitivity to immunotherapy. We sought to reproduce this phenotype using mutagenic agents to engineer an MMRd genotype in immunoresistant cells. The combination of temozolomide (TMZ) and cisplatin led to a rapid accumulation of a high mutational load enriched for indels in murine...
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