1. Genomic events stratifying prognosis of early gastric cancer.
- Author
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Molinari, Chiara, Solaini, Leonardo, Rebuzzi, Francesca, Tedaldi, Gianluca, Angeli, Davide, Petracci, Elisabetta, Prascevic, Dusan, Ewald, Jan, Rahm, Erhard, Canale, Matteo, Giovanni, Martinelli, Tomezzoli, Anna, Bencivenga, Maria, Ambrosio, Maria Raffaella, Marrelli, Daniele, Morgagni, Paolo, Ercolani, Giorgio, Ulivi, Paola, and Saragoni, Luca
- Subjects
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PROGRESSION-free survival , *STOMACH cancer , *GENETIC mutation , *STATISTICAL significance , *MICROSATELLITE repeats - Abstract
Background: The purpose of the study was to conduct a comprehensive genomic characterization of gene alterations, microsatellite instability (MSI), and tumor mutational burden (TMB) in submucosal-penetrating (Pen) early gastric cancers (EGCs) with varying prognoses. Methods: Samples from EGC patients undergoing surgery and with 10-year follow-up data available were collected. Tissue genomic alterations were characterized using Trusight Oncology panel (TSO500). Pathway instability (PI) scores for a selection of 218 GC-related pathways were calculated both for the present case series and EGCs from the TCGA cohort. Results: Higher age and tumor location in the upper-middle tract are significantly associated with an increased hazard of relapse or death from any cause (p = 0.006 and p = 0.032). Even if not reaching a statistical significance, Pen A tumors more frequently present higher TMB values, higher frequency of MSI-subtypes and an overall increase in PI scores, along with an enrichment in immune pathways. ARID1A gene was observed to be significantly more frequently mutated in Pen A tumors (p = 0.006), as well as in patients with high TMB (p = 0.027). Tumors harboring LRP1B alterations seem to have a higher hazard of relapse or death from any cause (p = 0.089), being mutated mainly in relapsed patients (p = 0.093). Conclusions: We found that the most aggressive subtype Pen A is characterized by a higher frequency of ARID1A mutations and a higher genetic instability, while LRP1B alterations seem to be related to a lower disease-free survival. Further investigations are needed to provide a rationale for the use of these markers to stratify prognosis in EGC patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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