Characterization of shared neoantigens landscape in Mismatch Repair Deficient Endometrial Cancer

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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Publication Details

Journal
npj Precision Oncology
Published
2024-12-20
DOI
https://doi.org/10.1038/s41698-024-00779-4
Citations
4
Primary Topic
Genetic factors in colorectal cancer
Type
article
Field-Weighted Citation Impact
1.70
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article

Characterization of shared neoantigens landscape in Mismatch Repair Deficient Endometrial Cancer

Elisa Scarselli, Elisa De Paolis, Elisa Micarelli, Gianfranco Zannoni et al.
4 citations
npj Precision Oncology
Genetic factors in colorectal cancer
1.70
article

Characterization of shared neoantigens landscape in Mismatch Repair Deficient Endometrial Cancer

Elisa Scarselli, Elisa De Paolis, Elisa Micarelli, Gianfranco Zannoni, Francesco Fanfani, Luciano Giacò, Giovanni Scambia, Anna Morena D’Alise, Andrea Urbani, Alessia Preziosi, Guido Leoni, Tina Pasciuto, Rita Trozzi, Camilla Nero, Gennaro Daniele, Angelo Minucci, Diletta Piana, Maria De Bonis, Alessia Piermattei
article en
4 citations

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.

npj Precision OncologyVol. 8(1)
Università Cattolica del Sacro Cuore (IT), Agostino Gemelli University Polyclinic (IT), Nouscom (Italy) (IT), University of the Sacred Heart (JP), Istituti di Ricovero e Cura a Carattere Scientifico (IT)
Zero hunger
Openalex Percentile: Top 15%
Genetic factors in colorectal cancer
1.70
DOIOpen Access PDFOpenAlex
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