Pubblicazioni

Autori:

Angerilli, Valentina; Sabella, Giovanna; Simbolo, Michele; Lagano, Vincenzo; Centonze, Giovanni; Gentili, Marco; Mangogna, Alessandro; Coppa, Jorgelina; Munari, Giada; Businello, Gianluca; Borga, Chiara; Schiavi, Francesca; Pusceddu, Sara; Leporati, Rita; Oldani, Simone; Fassan, Matteo; Milione, Massimo

Titolo:

Comprehensive genomic and transcriptomic characterization of high-grade gastro-entero-pancreatic neoplasms

Anno:

2024

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Referee:

No

Nome rivista:

British Journal of Cancer

ISSN Rivista:

0007-0920

N° Volume:

131

Numero o Fascicolo:

1

Intervallo pagine:

159-170

Parole chiave:

MIXED ADENONEUROENDOCRINE CARCINOMAS, NEUROENDOCRINE CARCINOMAS, PROGNOSTIC-FACTORS, G3, HETEROGENEITY, GUIDELINES, SURVIVAL, INSIGHTS, TUMORS

Breve descrizione dei contenuti:

Background High-grade gastro-entero-pancreatic neoplasms (HG GEP-NENs) can be stratified according to their morphology and Ki-67 values into three prognostic classes: neuroendocrine tumors grade 3 (NETs G3), neuroendocrine carcinomas with Ki-67 < 55% (NECs <55) and NECs with Ki-67 >= 55% (NECs >= 55). Methods We analyzed a cohort of 49 HG GEP-NENs by targeted Next-Generation Sequencing (TrueSight Oncology 500), RNA-seq, and immunohistochemistry for p53, Rb1, SSTR-2A, and PD-L1. Results Frequent genomic alterations affected TP53 (26%), APC (20%), KRAS and MEN1 (both 11%) genes. NET G3 were enriched in MEN1 (p = 0.02) mutations, while both NECs groups were enriched in TP53 (p = 0.001), APC (p = 0.002) and KRAS (p = 0.02) mutations and tumors with TMB >= 10 muts/Mb (p = 0.01). No differentially expressed (DE) gene was found between NECs <55% and NECs >= 55%, while 1129 DE genes were identified between NET G3 and NECs. A slight enrichment of CD4+ and CD8+ T cells in NECs and of cancer-associated fibroblasts and macrophages (M2-like) in NET G3. Multivariate analysis identified histologic type and Rb1 loss as independent prognostic factors for overall survival. Conclusions This study showed that GEP-NET G3 and GEP-NECs exhibit clear genomic and transcriptomic differences, differently from GEP-NECs <55% and GEP-NECs >= 55%, and provided molecular findings with prognostic and potentially predictive value.

Note:

Epub 2024 May 10 The online version contains supplementary material available at https://doi.org/10.1038/s41416-024-02705-8.

Pagina Web:

https://www.nature.com/articles/s41416-024-02705-8

Id prodotto:

140442

Handle IRIS:

11562/1130868

ultima modifica:

13 luglio 2024

Citazione bibliografica:

Angerilli, Valentina; Sabella, Giovanna; Simbolo, Michele; Lagano, Vincenzo; Centonze, Giovanni; Gentili, Marco; Mangogna, Alessandro; Coppa, Jorgelina; Munari, Giada; Businello, Gianluca; Borga, Chiara; Schiavi, Francesca; Pusceddu, Sara; Leporati, Rita; Oldani, Simone; Fassan, Matteo; Milione, Massimo, Comprehensive genomic and transcriptomic characterization of high-grade gastro-entero-pancreatic neoplasms «British Journal of Cancer» , vol. 131 , n. 1 , 2024 , pp. 159-170

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo