Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
 

Learn about the flu shot, COVID-19 vaccine, and our masking policy »

Stanford Health Care

Genomic and microenvironmental landscape of stage I follicular lymphoma, compared to stage III/IV. Blood advances Los-de Vries, G. T., Stevens, W. B., van Dijk, E. v., Langois-Jacques, C., Clear, A. J., Stathi, P., Roemer, M. G., Mendeville, M., Hijmering, N. J., Sander, B., Rosenwald, A., Calaminici, M., Hoster, E., Hiddemann, W., Gaulard, P., Salles, G. A., Horn, H., Klapper, W., Xerri, L., Burton, C., Tooze, R. M., Smith, A. G., Buske, C., Scott, D. W., Natkunam, Y., Advani, R., Sehn, L. H., Raemaekers, J. M., Gribben, J. G., Kimby, E. K., Kersten, M. J., Maucort-Boulch, D., Ylstra, B., de Jong, D. 2022

Abstract

While the genomic and immune microenvironmental landscape of follicular lymphoma (FL) has been extensively investigated, little is known regarding potential biological differences between stage I and stage III/IV disease. Using next generation sequencing (NGS) and immunohistochemistry, 82 FL nodal stage I cases were analysed and compared to 139 FL stage III/IV nodal cases. Many similarities in mutations, chromosomal copy number aberrations (CNAs) and microenvironmental cell populations were detected. However, there were also significant differences in microenvironmental and genomic features. CD8+ T-cells (p=0.02) and STAT6 mutations (FDR<0.001), were more frequent in stage I FL. In contrast, PD1+ T-cells, CD68+/CD163+ macrophages (p<0.001), BCL2 translocation (BCL2trl+) (p<0.0001), KMT2D (FDR=0.003) and CREBBP (FDR=0.04) mutations were found more frequently in stage III/IV FL. By clustering we identified three clusters within stage I, and two within stage III/IV. The BLC2trl+ stage I cluster was comparable to the BCL2trl+ cluster in stage III/IV. The two BCL2trl- stage I clusters were unique for stage I. One was enriched for CREBBP (95%) and STAT6 (64%) mutations, without BLC6 translocation (BCL6trl), whereas the BCL2trl- stage III/IV cluster contained BCL6trl (64%) with less CREBBP (45%) and STAT6 (9%) mutations. The other BCL2trl- stage I cluster was relatively heterogeneous with more CNAs and linker histone mutations. This exploratory study shows that FL stage I is genetically heterogenous with different underlying oncogenic pathways. Stage I FL BCL2trl- is likely STAT6 driven while BCL2trl- stage III/IV appears to be more BCL6trl driven.

View details for DOI 10.1182/bloodadvances.2022008355

View details for PubMedID 35816682