Genomic and microenvironmental landscape of stage I follicular lymphoma, compared with stage III/IV

Los-deVries, G. Tjitske; Stevens, Wendy B. C.; Dijk, Erik van; Langois-Jacques, Carole; Clear, Andrew J.; Stathi, Phylicia; Roemer, Margaretha G. M.; Mendeville, Matias; Hijmering, Nathalie J.; Sander, Birgitta; Rosenwald, Andreas; Calaminici, Maria; Hoster, Eva; Hiddemann, Wolfgang; Gaulard, Philippe; Salles, Gilles; Horn, Heike; Klapper, Wolfram; Xerri, Luc; Burton, Catherine; Tooze, Reuben M.; Smith, Alexandra G.; Buske, Christian; Scott, David W.; Natkunam, Yasodha; Advani, Ranjana; Sehn, Laurie H.; Raemaekers, John; Gribben, John; Kimby, Eva; Kersten, Marie Jose; Maucort-Boulch, Delphine; Ylstra, Bauke und Jong, Daphne de (2022): Genomic and microenvironmental landscape of stage I follicular lymphoma, compared with stage III/IV. In: Blood Advances, Bd. 6, Nr. 18: S. 5482-5493

Abstract

Although the genomic and immune microenvironmental landscape of follicular lymphoma (FL) has been extensively investigated, little is known about the potential biological differences between stage I and stage III/IV disease. Using next-generation sequencing and immunohistochemistry, 82 FL nodal stage I cases were analyzed and compared with 139 FL stage III/IV nodal cases. Many similarities in mutations, chromosomal copy number aberrations, and microenvironmental cell populations were detected. However, there were also significant differences in microenvironmental and genomic features. CD8+ T cells (P = .02) and STAT6 mutations (false discovery rate [FDR] <0.001) were more frequent in stage I FL. In contrast, programmed cell death protein 1-positive T cells, CD68+/CD163+ macrophages (P < .001), BCL2 translocation (BCL2trl+) (P < .0001), and KMT2D (FDR = 0.003) and CREBBP (FDR = 0.04) mutations were found more frequently in stage III/IV FL. Using clustering, we identified 3 clusters within stage I, and 2 clusters 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 fewer CREBBP (45%) and STATE (9%) mutations. The other BCL2trl- stage I cluster was relatively heterogeneous with more copy number aberrations and linker histone mutations. This exploratory study shows that stage I FL is genetically heterogeneous with different underlying oncogenic pathways. Stage I FL BCL2trl- is likely STAT6 driven, whereas BCL2trl- stage III/IV appears to be more BCL6trl driven.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2473-9529
• Sprache: Englisch