Clonal heterogeneity of lymphoid malignancies correlates with poor prognosis

Cancer Sci. 2014 Jul;105(7):897-904. doi: 10.1111/cas.12442. Epub 2014 Jul 1.

Abstract

Clonal heterogeneity in lymphoid malignancies has been recently reported in adult T-cell lymphoma/leukemia, peripheral T-cell lymphoma, not otherwise specified, and mantle cell lymphoma. Our analysis was extended to other types of lymphoma including marginal zone lymphoma, follicular lymphoma and diffuse large B-cell lymphoma. To determine the presence of clonal heterogeneity, 332 cases were examined using array comparative genomic hybridization analysis. Results showed that incidence of clonal heterogeneity varied from 25% to 69% among different types of lymphoma. Survival analysis revealed that mantle cell lymphoma and diffuse large B-cell lymphoma with clonal heterogeneity showed significantly poorer prognosis, and that clonal heterogeneity was confirmed as an independent predictor of poor prognosis for both types of lymphoma. Interestingly, 8q24.1 (MYC) gain, 9p21.3 (CDKN2A/2B) loss and 17p13 (TP53, ATP1B2, SAT2, SHBG) loss were recurrent genomic lesions among various types of lymphoma with clonal heterogeneity, suggesting at least in part that alterations of these genes may play a role in clonal heterogeneity.

Keywords: Array comparative genomic hybridization; heterogeneity; malignant lymphoma; patient outcome assessment; tumor cell population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Burkitt Lymphoma / genetics
  • Burkitt Lymphoma / mortality
  • Burkitt Lymphoma / pathology
  • Chromosomes, Human, Pair 8
  • Comparative Genomic Hybridization
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Gene Deletion
  • Gene Dosage
  • Humans
  • Lymphoma / genetics*
  • Lymphoma / mortality*
  • Lymphoma / pathology*
  • Lymphoma, B-Cell, Marginal Zone / genetics
  • Lymphoma, B-Cell, Marginal Zone / mortality
  • Lymphoma, B-Cell, Marginal Zone / pathology
  • Lymphoma, Follicular / genetics
  • Lymphoma, Follicular / mortality
  • Lymphoma, Follicular / pathology
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Prognosis

Substances

  • Cyclin-Dependent Kinase Inhibitor p16

Associated data

  • GEO/GSE35278
  • GEO/GSE54303