Endometrial cancer (EC) with Mismatch Repair deficiency (MMRd) is characterized by the accumulation of insertions/deletions at microsatellite sites. These mutations lead to the synthesis of frameshift peptides (FSPs) that represent tumor-specific neoantigens (nAg) proved to be shared across patients/tumors with MMRd. In this study, we explored the feasibility of a nAg-based cancer vaccination design in EC with MMRd. We adopted a whole exome sequencing approach and ad hoc bioinformatics pipelines to characterize FSPs in 35 patients with EC. A mean of 146 mutated mononucleotide repeats (MNRs) was identified with enrichment in the patients' group with MLH1 impairment. A high coverage emerged from the comparative analysis of the EC FSPs with the content of the previously validated NOUS-209 vaccine. We obtained pieces of evidence of FSPs translation as expressed proteins from Ribo-seq, supporting the potential as the target of vaccination. The development of a nAgs-based vaccine strategy in MMRd EC may be further explored.
De Paolis, E., Nero, C., Micarelli, E., Leoni, G., Piermattei, A., Trozzi, R., Scarselli, E., D'Alise, A., Giacò, L., De Bonis, M., Preziosi, A., Daniele, G., Piana, D., Pasciuto, T., Zannoni, G. F., Minucci, A., Scambia, G., Urbani, A., Fanfani, F., Characterization of shared neoantigens landscape in Mismatch Repair Deficient Endometrial Cancer, <<NPJ PRECISION ONCOLOGY>>, 2024; 8 (1): 1-9. [doi:10.1038/s41698-024-00779-4] [https://hdl.handle.net/10807/314598]
Characterization of shared neoantigens landscape in Mismatch Repair Deficient Endometrial Cancer
De Paolis, Elisa;Nero, Camilla;Leoni, Giulia;Piermattei, Angelo;Trozzi, Rita;Daniele, Gennaro;Piana, Diletta;Pasciuto, Tina;Zannoni, Gian Franco;Minucci, Angelo;Scambia, Giovanni;Urbani, Andrea
;Fanfani, Francesco
2024
Abstract
Endometrial cancer (EC) with Mismatch Repair deficiency (MMRd) is characterized by the accumulation of insertions/deletions at microsatellite sites. These mutations lead to the synthesis of frameshift peptides (FSPs) that represent tumor-specific neoantigens (nAg) proved to be shared across patients/tumors with MMRd. In this study, we explored the feasibility of a nAg-based cancer vaccination design in EC with MMRd. We adopted a whole exome sequencing approach and ad hoc bioinformatics pipelines to characterize FSPs in 35 patients with EC. A mean of 146 mutated mononucleotide repeats (MNRs) was identified with enrichment in the patients' group with MLH1 impairment. A high coverage emerged from the comparative analysis of the EC FSPs with the content of the previously validated NOUS-209 vaccine. We obtained pieces of evidence of FSPs translation as expressed proteins from Ribo-seq, supporting the potential as the target of vaccination. The development of a nAgs-based vaccine strategy in MMRd EC may be further explored.
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