GRCh37 · COSMIC v92

Summary

This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

Reference
Deep sequencing identifies genetic heterogeneity and recurrent convergent evolution in chronic lymphocytic leukemia.
Paper ID
COSP37715
Authors
Ojha J, Ayres J, Secreto C, Tschumper R, Rabe K, Van Dyke D, Slager S, Shanafelt T, Fonseca R, Kay NE and Braggio E
Affiliation
Mayo Clinic, Scottsdale, AZ;
Journal
Blood, 2015;125(3):492-8
ISSN: 1528-0020
PMID: 25377784 (view at PubMed or Europe PMC)
Abstract
Recent high-throughput sequencing and microarray studies have characterized the genetic landscape and clonal complexity of chronic lymphocytic leukemia (CLL). Here, we performed a longitudinal study in a homogeneously treated cohort of 12 patients, with sequential samples obtained at comparable stages of disease. We identified clonal competition between 2 or more genetic subclones in 70% of the patients with relapse, and stable clonal dynamics in the remaining 30%. 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 patients, 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.
Paper Status
Curated