A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma

Blood. 2014 Feb 20;123(8):1187-98. doi: 10.1182/blood-2013-06-507996. Epub 2014 Jan 7.

Abstract

The genetic hallmark of Burkitt lymphoma (BL) is the t(8;14)(q24;q32) and its variants leading to activation of the MYC oncogene. It is a matter of debate whether true BL without MYC translocation exists. Here, we identified 59 lymphomas concordantly called BL by 2 gene expression classifiers among 753 B-cell lymphomas. Only 2 (3%) of these 59 molecular BL lacked a MYC translocation, which both shared a peculiar pattern of chromosome 11q aberration characterized by interstitial gains including 11q23.2-q23.3 and telomeric losses of 11q24.1-qter. We extended our analysis to 17 MYC-negative high-grade B-cell lymphomas with a similar 11q aberration and showed this aberration to be recurrently associated with morphologic and clinical features of BL. The minimal region of gain was defined by high-level amplifications in 11q23.3 and associated with overexpression of genes including PAFAH1B2 on a transcriptional and protein level. The recurrent region of loss contained a focal homozygous deletion in 11q24.2-q24.3 including the ETS1 gene, which was shown to be mutated in 4 of 16 investigated cases. These findings indicate the existence of a molecularly distinct subset of B-cell lymphomas reminiscent of BL, which is characterized by deregulation of genes in 11q.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • B-Lymphocytes / physiology*
  • Burkitt Lymphoma / classification*
  • Burkitt Lymphoma / genetics*
  • Burkitt Lymphoma / pathology
  • Cell Line
  • Child
  • Chromosomes, Human, Pair 11
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 8
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, myc / genetics*
  • Humans
  • Male
  • Neoplasm Grading
  • Recurrence
  • Translocation, Genetic / genetics*
  • Young Adult