We applied digital spatial profiling for 87 immune and stromal genes to lymph node germinal center (GC) dark- and light-zone (DZ/LZ) regions of interest to obtain a differential signature of these two distinct microenvironments. The spatially resolved 53-genes signature, comprising key genes of the DZmutational machinery and LZ immune and mesenchymal milieu, was applied to the transcriptomes of 543 GC-related diffuse large B cell lymphomas and double-hit ( DH) lymphomas. According to the DZ/LZ signature, the GC-related lymphomas were sub-classified into two clusters. The subgroups differed in the distribution of DH cases and survival, with most DH displaying a distinct DZ-like profile. The clustering analysis was also performed using a 25-genes signature composed of genes positively enriched in the non-B, stromal sub-compartments, for the first time achieving DZ/LZ discrimination based on stromal/immune features. The report offers new insight into the GC microenvironment, hinting at a DZ microenvironment of origin in DH lymphomas.

A Spatially Resolved Dark- versus Light-Zone Microenvironment Signature Subdivides Germinal Center-Related Aggressive B Cell Lymphomas

Mangogna, Alessandro
Writing – Review & Editing
;
2020

Abstract

We applied digital spatial profiling for 87 immune and stromal genes to lymph node germinal center (GC) dark- and light-zone (DZ/LZ) regions of interest to obtain a differential signature of these two distinct microenvironments. The spatially resolved 53-genes signature, comprising key genes of the DZmutational machinery and LZ immune and mesenchymal milieu, was applied to the transcriptomes of 543 GC-related diffuse large B cell lymphomas and double-hit ( DH) lymphomas. According to the DZ/LZ signature, the GC-related lymphomas were sub-classified into two clusters. The subgroups differed in the distribution of DH cases and survival, with most DH displaying a distinct DZ-like profile. The clustering analysis was also performed using a 25-genes signature composed of genes positively enriched in the non-B, stromal sub-compartments, for the first time achieving DZ/LZ discrimination based on stromal/immune features. The report offers new insight into the GC microenvironment, hinting at a DZ microenvironment of origin in DH lymphomas.
16-set-2020
Pubblicato
https://www.sciencedirect.com/science/article/pii/S2589004220307549?via=ihub
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522121/
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S2589004220307549-main.pdf

accesso aperto

Tipologia: Documento in Versione Editoriale
Licenza: Creative commons
Dimensione 6.1 MB
Formato Adobe PDF
6.1 MB Adobe PDF Visualizza/Apri
1-s2.0-S2589004220307549-mmc1.pdf

accesso aperto

Descrizione: Supplementary information
Tipologia: Altro materiale allegato
Licenza: Digital Rights Management non definito
Dimensione 1.39 MB
Formato Adobe PDF
1.39 MB Adobe PDF Visualizza/Apri
1-s2.0-S2589004220307549-mmc2.xlsx

accesso aperto

Descrizione: Supplementary table 1
Tipologia: Altro materiale allegato
Licenza: Digital Rights Management non definito
Dimensione 16.27 kB
Formato Microsoft Excel XML
16.27 kB Microsoft Excel XML Visualizza/Apri
1-s2.0-S2589004220307549-mmc3.xlsx

accesso aperto

Descrizione: Supplementary table 2
Tipologia: Altro materiale allegato
Licenza: Digital Rights Management non definito
Dimensione 12.31 kB
Formato Microsoft Excel XML
12.31 kB Microsoft Excel XML Visualizza/Apri
1-s2.0-S2589004220307549-mmc4.xlsx

accesso aperto

Descrizione: Supplementary table 3
Tipologia: Altro materiale allegato
Licenza: Digital Rights Management non definito
Dimensione 13.02 kB
Formato Microsoft Excel XML
13.02 kB Microsoft Excel XML Visualizza/Apri
1-s2.0-S2589004220307549-mmc5.xlsx

accesso aperto

Descrizione: Supplementary table 4
Tipologia: Altro materiale allegato
Licenza: Digital Rights Management non definito
Dimensione 60.79 kB
Formato Microsoft Excel XML
60.79 kB Microsoft Excel XML 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/11368/3025078
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 13
social impact