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...

Full description

Saved in:
Bibliographic Details
Published in:NPJ precision oncology 2024-12, Vol.8 (1), p.283-9
Main Authors: De Paolis, Elisa, Nero, Camilla, Micarelli, Elisa, Leoni, Guido, Piermattei, Alessia, Trozzi, Rita, Scarselli, Elisa, D’Alise, Anna Morena, Giacò, Luciano, De Bonis, Maria, Preziosi, Alessia, Daniele, Gennaro, Piana, Diletta, Pasciuto, Tina, Zannoni, Gianfranco, Minucci, Angelo, Scambia, Giovanni, Urbani, Andrea, Fanfani, Francesco
Format: Article
Language:English
Subjects:
631/67/1517/1931
692/4017
Cancer Research
Endometrial cancer
Gene Therapy
Human Genetics
Immunization
Internal Medicine
Medicine
Medicine & Public Health
Oncology
Vaccines
Yeast
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2397-768X
2397-768X
DOI:10.1038/s41698-024-00779-4