Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cell. 2013 Feb 14;152(4):714-26. doi: 10.1016/j.cell.2013.01.019.

Evolution and impact of subclonal mutations in chronic lymphocytic leukemia.

Author information

  • 1Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

Abstract

Clonal 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.

Copyright © 2013 Elsevier Inc. All rights reserved.

Comment in

PMID:
23415222
[PubMed - indexed for MEDLINE]
PMCID:
PMC3575604
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk