Deep sequencing identifies genetic heterogeneity and recurrent convergent evolution in chronic lymphocytic leukemia
Menée de façon longitudinale sur 12 patients atteints d'une leucémie lymphocytaire chronique, cette étude identifie une importante hétérogénéité génétique entre diverses sous-populations clonales et, pour deux patients, un phénomène de convergence évolutive entre plusieurs sous-populations clonales
Recent high throughput sequencing and microarray studies have characterized the genetic landscape and clonal complexity of CLL. In this study we performed a longitudinal study in a homogeneously treated cohort of 12 cases with sequential samples at comparable stages of disease. We identified clonal competition between 2 or more genetic subclones in 70% of the cases with relapse and stable clonal dynamics in the remaining 30% of the cases. By deep sequencing, we identified a high reservoir of genetic heterogeneity in the form of several driver genes mutated in small subclones underlying the disease course. Furthermore, in 2 cases, we identified convergent evolution, characterized by the combination of genetic lesions affecting the same genes or copy number abnormality in different subclones. The phenomenon affects multiple CLL putative driver abnormalities, including mutations in NOTCH1, SF3B1, DDX3X and del(11q23). This is the first report documenting convergent evolution as a recurrent event in the CLL genome. Furthermore, this finding suggests the selective advantage of specific combinations of genetic lesions for CLL pathogenesis in a subset of patients.