Skip NavigationSkip to Content

Combined somatic mutation and copy number analysis in the survival of familial CLL

  1. Author:
    Zhou, Weiyin
    Goldin, Lynn [ORCID]
    Wang, Mingyi
    McMaster, Mary L
    Jones, Kristine
    Burdett, Laurie
    Chanock, Stephen J
    Yeager, Meredith
    Dean, Michael [ORCID]
    Caporaso, Neil E
  2. Author Address

    Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, 21702, USA., Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland, 20892, USA.,
    1. Year: 2018
    2. Date: Jun
    3. Epub Date: 2018 04 24
  1. Journal: British Journal of Haematology
    1. 181
    2. 5
    3. Pages: 604-613
  2. Type of Article: Article
  3. ISSN: 0007-1048
  1. Abstract:

    Recurrent large-scale somatic copy number alterations (SCNAs), and somatic point mutations can be analysed to stratify patients with chronic lymphocytic leukaemia (CLL) into distinct prognostic groups. To investigate the relationship between SCNAs and somatic mutations, we performed whole-exome sequencing and single nucleotide polymorphism microarray analyses on 98 CLL patients from 40 families with a high burden of CLL. Overall, 69 somatic mutations in 29 CLL driver genes were detected among 45 subjects (46%), with the most frequently mutated genes being TP53 (8·2%), NOTCH1 (8·2%) and ATM (5·1%). Additionally, 142 SCNAs from 54 subjects (57%) were detected, including losses of chromosome 13q14 (28·9%), 11q (5·6%), 17p (2·1%), and gain of chromosome 12 (4·2%). We found that patients having both an adverse point mutation in a CLL driver gene and an unfavourable SCNA tended to have poorer survival (Hazard ratio [HR] = 3·17, 95% confidence interval [CI] = 0·97-10·35; P = 0·056) than patients having either a point mutation (HR = 1·34, 95%CI = 0·66-2·71; P = 0·42) or SCNAs (HR = 2·65, 95%CI = 0·77-9·13; P = 0·12). TP53 mutation carriers were associated with the poorest overall survival (HR = 4·39, 95%CI = 1·28-15·04; P = 0·018). Our study suggests that combining SCNA and mutational data could contribute to predicting outcome in familial CLL. © 2018 John Wiley & Sons Ltd.

    See More

External Sources

  1. DOI: 10.1111/bjh.15239
  2. PMID: 29687880
  3. WOS: 000433333100006

Library Notes

  1. Fiscal Year: FY2017-2018
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel