Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma

Okosun, J ✉; Bödör, C* ✉ [Bödör, Csaba (Molekuláris Onkoh...), szerző] I. Sz. Patológiai és Kísérleti Rákkutató Intézet (SE / AOK / I); Wang, J*; Araf, S; Yang, C-Y; Pan, C; Boller, S; Cittaro, D; Bozek, M; Iqbal, S; Matthews, J; Wrench, D; Marzec, J; Tawana, K; Popov, N; O'Riain, C; O'Shea, D; Carlotti, E; Davies, A; Lawrie, CH; Matolcsy, A [Matolcsy, András (Pathológia), szerző] I. Sz. Patológiai és Kísérleti Rákkutató Intézet (SE / AOK / I); Calaminici, M; Norton, A; Byers, RJ; Mein, C; Stupka, E; Lister, TA; Lenz, G; Montoto, S; Gribben, JG; Fan, Y; Grosschedl, R; Chelala, C; Fitzgibbon, J

Angol nyelvű Sokszerzős vagy csoportos szerzőségű szakcikk (Folyóiratcikk) Tudományos
Megjelent: NATURE GENETICS 1061-4036 1546-1718 46 (2) pp. 176-181 2014
  • SJR Scopus - Genetics: D1
Azonosítók
Szakterületek:
  • Biológiai tudományok
Follicular lymphoma is an incurable malignancy, with transformation to an aggressive subtype representing a critical event during disease progression. Here we performed whole-genome or whole-exome sequencing on 10 follicular lymphoma-transformed follicular lymphoma pairs followed by deep sequencing of 28 genes in an extension cohort, and we report the key events and evolutionary processes governing tumor initiation and transformation. Tumor evolution occurred through either a 'rich' or 'sparse' ancestral common progenitor clone (CPC). We identified recurrent mutations in linker histone, JAK-STAT signaling, NF-κB signaling and B cell developmental genes. Longitudinal analyses identified early driver mutations in chromatin regulator genes (CREBBP, EZH2 and KMT2D (MLL2)), whereas mutations in EBF1 and regulators of NF-κB signaling (MYD88 and TNFAIP3) were gained at transformation. Collectively, this study provides new insights into the genetic basis of follicular lymphoma and the clonal dynamics of transformation and suggests that personalizing therapies to target key genetic alterations in the CPC represents an attractive therapeutic strategy.
Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSLMásolásNyomtatás
2024-07-25 02:11