Whole-genome analysis and HLA genotyping of enteropathy-type T-cell lymphoma reveals 2 distinct lymphoma subtypes

Gastroenterology. 2007 May;132(5):1902-11. doi: 10.1053/j.gastro.2007.03.036. Epub 2007 Mar 24.


Background & aims: Enteropathy-type T-cell lymphoma (ETL) is an aggressive extranodal T-cell non-Hodgkin lymphoma assumed to arise in the setting of celiac disease.

Methods: To precisely define the genetic alterations underlying the pathogenesis of ETL, 30 ETL samples were profiled for genetic copy number alterations using high-resolution whole-genome tiling path array comparative genomic hybridization. To investigate the potential association of genetic alterations in ETL with celiac disease, HLA-DQB1 genotyping was performed.

Results: By array comparative genomic hybridization, 13 novel recurrent minimal regions of chromosomal alteration were identified on multiple chromosome arms. ETL is characterized by frequent complex gains of 9q31.3-qter (70% of cases), or by an almost mutually exclusive 2.5-megabase loss of 16q12.1 (23% of cases). Two distinct groups of ETL could be delineated morphologically and genetically: type 1 ETL is characterized by nonmonomorphic cytomorphology, CD56 negativity, and chromosomal gains of 1q and 5q. Type 1 ETL also appears to be linked pathogenetically to celiac disease, sharing genetic alterations and HLA-DQB1 genotype patterns with (refractory) celiac disease. Type 2 ETL shows monomorphic small- to medium-sized tumor cell morphology, frequently shows CD56 expression, MYC oncogene locus gain, and rare gains of chromosomes 1q and 5q. In contrast to type 1 ETL, type 2 ETL shows a HLA-DQB1 genotype pattern more resembling that of the normal Caucasian population.

Conclusions: Contrary to current clinical classification, ETL comprises 2 morphologically, clinically, and genetically distinct lymphoma entities. In addition, type 2 ETL may not be associated with celiac disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CD56 Antigen / genetics
  • CD56 Antigen / metabolism
  • CD8 Antigens / genetics
  • CD8 Antigens / metabolism
  • Celiac Disease / complications
  • Celiac Disease / genetics*
  • Celiac Disease / physiopathology
  • Chromosome Mapping
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 5 / genetics
  • DNA, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genome, Human / genetics*
  • Genotype
  • HLA-DQ Antigens / genetics*
  • HLA-DQ Antigens / metabolism
  • HLA-DQ beta-Chains
  • Humans
  • Lymphoma, T-Cell / classification*
  • Lymphoma, T-Cell / etiology
  • Lymphoma, T-Cell / genetics*
  • Male
  • Middle Aged


  • CD56 Antigen
  • CD8 Antigens
  • DNA, Neoplasm
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQ2 antigen
  • HLA-DQ8 antigen
  • HLA-DQB1 antigen