Scientific Publications

Evolution and impact of subclonal mutations in chronic lymphocytic leukemia.

Publication TypeJournal Article
AuthorsLandau, DA, Carter SL, Stojanov P., McKenna A., Stevenson K., Lawrence MS, Sougnez C., Stewart C., Sivachenko A., Wang L., Wan Y., Zhang W., Shukla SA, Vartanov A., Fernandes SM, Saksena G., Cibulskis K., Tesar B., Gabriel S., Hacohen N., Meyerson M., Lander E. S., Neuberg D., Brown JR, Getz G., and Wu CJ
AbstractClonal evolution is a key feature of cancer progression and relapse. We studied intratumoral heterogeneity in 149 chronic lymphocytic leukemia (CLL) cases by integrating whole-exome sequence and copy number to measure the fraction of cancer cells harboring each somatic mutation. We identified driver mutations as predominantly clonal (e.g., MYD88, trisomy 12, and del(13q)) or subclonal (e.g., SF3B1 and TP53), corresponding to earlier and later events in CLL evolution. We sampled leukemia cells from 18 patients at two time points. Ten of twelve CLL cases treated with chemotherapy (but only one of six without treatment) underwent clonal evolution, predominantly involving subclones with driver mutations (e.g., SF3B1 and TP53) that expanded over time. Furthermore, presence of a subclonal driver mutation was an independent risk factor for rapid disease progression. Our study thus uncovers patterns of clonal evolution in CLL, providing insights into its stepwise transformation, and links the presence of subclones with adverse clinical outcomes.
Year of Publication2013
JournalCell
Volume152
Issue4
Pages714-26
Date Published (YYYY/MM/DD)2013/02/14
ISSN Number0092-8674
DOI10.1016/j.cell.2013.01.019
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/23415222?dopt=Abstract