Recurrent loss of heterozygosity in 1p36 associated with TNFRSF14 mutations in IRF4 translocation negative pediatric follicular lymphomas

Haematologica. 2013 Aug;98(8):1237-41. doi: 10.3324/haematol.2012.073916. Epub 2013 Feb 26.

Abstract

Pediatric follicular lymphoma is a rare disease that differs genetically and clinically from its adult counterpart. With the exception of pediatric follicular lymphoma with IRF4-translocation, the genetic events associated with these lymphomas have not yet been defined. We applied array-comparative genomic hybridization and molecular inversion probe assay analyses to formalin-fixed paraffin-embedded tissues from 18 patients aged 18 years and under with IRF4 translocation negative follicular lymphoma. All evaluable cases lacked t(14;18). Only 6 of 16 evaluable cases displayed chromosomal imbalances with gains or amplifications of 6pter-p24.3 (including IRF4) and deletion and copy number neutral-loss of heterozygosity in 1p36 (including TNFRSF14) being most frequent. Sequencing of TNFRSF14 located in the minimal region of loss in 1p36.32 showed nine mutations in 7 cases from our series. Two subsets of pediatric follicular lymphoma were delineated according to the presence of molecular alterations, one with genomic aberrations associated with higher grade and/or diffuse large B-cell lymphoma component and more widespread disease, and another one lacking genetic alterations associated with more limited disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Chromosome Deletion
  • Chromosome Disorders / diagnosis
  • Chromosome Disorders / genetics*
  • Chromosomes, Human, Pair 1 / genetics
  • Female
  • Follow-Up Studies
  • Humans
  • Interferon Regulatory Factors / genetics*
  • Loss of Heterozygosity / genetics*
  • Lymphoma, Follicular / diagnosis
  • Lymphoma, Follicular / genetics*
  • Male
  • Mutation / genetics
  • Receptors, Tumor Necrosis Factor, Member 14 / genetics*
  • Recurrence
  • Translocation, Genetic / genetics*

Substances

  • Interferon Regulatory Factors
  • Receptors, Tumor Necrosis Factor, Member 14
  • TNFRSF14 protein, human
  • interferon regulatory factor-4

Supplementary concepts

  • Chromosome 1p36 Deletion Syndrome