%0 Journal Article %1 Molinari2024-hq %A Molinari, Chiara %A Solaini, Leonardo %A Rebuzzi, Francesca %A Tedaldi, Gianluca %A Angeli, Davide %A Petracci, Elisabetta %A Prascevic, Dusan %A Ewald, Jan %A Rahm, Erhard %A Canale, Matteo %A Giovanni, Martinelli %A Tomezzoli, Anna %A Bencivenga, Maria %A Ambrosio, Maria Raffaella %A Marrelli, Daniele %A Morgagni, Paolo %A Ercolani, Giorgio %A Ulivi, Paola %A Saragoni, Luca %D 2024 %I Springer Science and Business Media LLC %J Gastric Cancer %K ARID1A EGC; LRP1B Pen; Prognosis %N 6 %P 1189--1200 %T Genomic events stratifying prognosis of early gastric cancer %V 27 %X 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.

@article{Molinari2024-hq, 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.}, added-at = {2024-11-12T14:03:24.000+0100}, author = {Molinari, Chiara and Solaini, Leonardo and Rebuzzi, Francesca and Tedaldi, Gianluca and Angeli, Davide and Petracci, Elisabetta and Prascevic, Dusan and Ewald, Jan and Rahm, Erhard and Canale, Matteo and Giovanni, Martinelli and Tomezzoli, Anna and Bencivenga, Maria and Ambrosio, Maria Raffaella and Marrelli, Daniele and Morgagni, Paolo and Ercolani, Giorgio and Ulivi, Paola and Saragoni, Luca}, biburl = {https://puma.scadsai.uni-leipzig.de/bibtex/2b8d0a2ba287dc64c6788781b0a0fd54f/scadsfct}, copyright = {https://creativecommons.org/licenses/by/4.0}, interhash = {3940e08d2ace22d60c293a2e18bbac47}, intrahash = {b8d0a2ba287dc64c6788781b0a0fd54f}, journal = {Gastric Cancer}, keywords = {ARID1A EGC; LRP1B Pen; Prognosis}, language = {en}, month = nov, number = 6, pages = {1189--1200}, publisher = {Springer Science and Business Media LLC}, timestamp = {2024-11-12T14:03:24.000+0100}, title = {Genomic events stratifying prognosis of early gastric cancer}, volume = 27, year = 2024 }