Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma
By J. Okosun, Csaba Bödör, Jun Wang, S. Araf, Cheng-Yuan Yang, C. Pan, S. Boller, Davide Cittaro, M. Bożek, S. Iqbal and 24 more. Nature Genetics, 2013
807 citations recorded by the source corpus.
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.
Subfields: Cancer Research, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/b6d318c62c70291744e44235119885f89649984a
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In Cancer Research
Citations in the corpus
- The 2016 revision of the World Health Organization classification of lymphoid neoplasms. (2016, neutral): “EZH2mutations, present in about 20% to 25%of FL, are another early event and potential therapeutic target.(57,58,60) Mutations are present in a large number of other genes, including some seen predominantly with transformation, but in significantly lower proportions Table 2.”
- Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future. (2017, neutral): “…et al., 2016), distinct AR amplification events in prostate cancer (Gundem et al., 2015), KMTD2D and CREBBP mutations in follicular lymphoma (Okosun et al., 2014) and PTEN and TP53 mutations, FGFR2 amplifications and RUNX1 deletions in primary breast cancer(Yates et al., 2015), as well as…”
- Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. (2015, background): “…and CREBBP occurring independently in two patients with follicular lymphoma and their paired transformed follicular lymphomas, occurring later in the disease course, suggest critical dependencies on mutational events in these genes for tumor maintenance or progression (Okosun et al., 2014).”