Pancreatic neuroendocrine tumors (PanNETs) display variable aggressive behavior. A major predictor of survival is tumor grade based on the Ki67 proliferation index. As information on transcriptomic profiles of PanNETs with different tumor grades is limited, we investigated 29 PanNETs (17 G1, 7 G2, 5 G3) for their expression profiles, mutations in 16 PanNET relevant genes and LINE‐1 DNA methylation profiles. A total of 3050 genes were differentially expressed between tumors with different grades (p < 0.05): 1279 in G3 vs. G2; 2757 in G3 vs. G1; and 203 in G2 vs. G1. Mutational analysis showed 57 alterations in 11 genes, the most frequent being MEN1 (18/29), DAXX (7/29), ATRX (6/29) and MUTYH (5/29). The presence and type of mutations did not correlate with the specific expression profiles associated with different grades. LINE‐1 showed significantly lower methylation in G2/G3 versus G1 tumors (p = 0.007). The expression profiles of matched primaries and metastasis (nodal, hepatic and colorectal wall) of three cases confirmed the role of Ki67 in defining specific expression profiles, which clustered according to tumor grades, independently from anatomic location or patient of origin. Such data call for future exploration of the role of Ki67 in tumor progression, given its involvement in chromosomal stability.

Simbolo, M., Bilotta, M., Mafficini, A., Luchini, C., Furlan, D., Inzani, F., Petrone, G., Bonvissuto, D., Rosa, S. L., Schinzari, G., Bianchi, A., Rossi, E., Menghi, R., Giuliante, F., Boccia, S., Scarpa, A., Rindi, G., Gene expression profiling of pancreas neuroendocrine tumors with different ki67‐based grades, <<CANCERS>>, 2021; 13 (9): 1-13. [doi:10.3390/cancers13092054] [http://hdl.handle.net/10807/185680]

Gene expression profiling of pancreas neuroendocrine tumors with different ki67‐based grades

Inzani, F.;Petrone, G.;Bonvissuto, D.;Schinzari, G.;Menghi, R.;Giuliante, F.;Boccia, S.;Rindi, G.
2021

Abstract

Pancreatic neuroendocrine tumors (PanNETs) display variable aggressive behavior. A major predictor of survival is tumor grade based on the Ki67 proliferation index. As information on transcriptomic profiles of PanNETs with different tumor grades is limited, we investigated 29 PanNETs (17 G1, 7 G2, 5 G3) for their expression profiles, mutations in 16 PanNET relevant genes and LINE‐1 DNA methylation profiles. A total of 3050 genes were differentially expressed between tumors with different grades (p < 0.05): 1279 in G3 vs. G2; 2757 in G3 vs. G1; and 203 in G2 vs. G1. Mutational analysis showed 57 alterations in 11 genes, the most frequent being MEN1 (18/29), DAXX (7/29), ATRX (6/29) and MUTYH (5/29). The presence and type of mutations did not correlate with the specific expression profiles associated with different grades. LINE‐1 showed significantly lower methylation in G2/G3 versus G1 tumors (p = 0.007). The expression profiles of matched primaries and metastasis (nodal, hepatic and colorectal wall) of three cases confirmed the role of Ki67 in defining specific expression profiles, which clustered according to tumor grades, independently from anatomic location or patient of origin. Such data call for future exploration of the role of Ki67 in tumor progression, given its involvement in chromosomal stability.
Inglese
Simbolo, M., Bilotta, M., Mafficini, A., Luchini, C., Furlan, D., Inzani, F., Petrone, G., Bonvissuto, D., Rosa, S. L., Schinzari, G., Bianchi, A., Rossi, E., Menghi, R., Giuliante, F., Boccia, S., Scarpa, A., Rindi, G., Gene expression profiling of pancreas neuroendocrine tumors with different ki67‐based grades, <<CANCERS>>, 2021; 13 (9): 1-13. [doi:10.3390/cancers13092054] [http://hdl.handle.net/10807/185680]
File in questo prodotto:
File Dimensione Formato  
Simbolo Cancers 2021.pdf

accesso aperto

Tipologia file ?: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 1.85 MB
Formato Adobe PDF
1.85 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/185680
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 2
social impact