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Updated: Jun 19, 2026

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Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2

Andrea B Moffitt1,2, Sarah L Ondrejka3, Matthew McKinney2

  • 1Duke Center for Genomics and Computational Biology, Duke University, Durham, NC 27708.

The Journal of Experimental Medicine
|April 21, 2017
PubMed

Insights

Enteropathy-associated T cell lymphoma (EATL), a lethal celiac disease complication, shows frequent SETD2 gene silencing and JAK-STAT pathway mutations. SETD2 loss impacts T cell development and lymphomagenesis.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Enteropathy-associated T cell lymphoma (EATL) is a rare but aggressive gastrointestinal malignancy.
  • EATL is the most common neoplastic complication of celiac disease, a chronic autoimmune disorder.
  • Understanding the genetic underpinnings of EATL is crucial for developing targeted therapies.

Purpose of the Study:

  • To define the comprehensive genetic landscape of EATL.
  • To identify frequently altered genes and pathways in EATL pathogenesis.
  • To investigate the role of SETD2 in T cell development and lymphomagenesis.

Main Methods:

  • Whole-exome sequencing was performed on 69 EATL tumor samples.
  • Genetic alterations in key pathways, including JAK-STAT, were analyzed.
  • A T cell-specific SETD2 knockout mouse model was developed to study its in vivo effects.

Main Results:

  • SETD2 was the most frequently silenced gene (32% of cases).
  • The JAK-STAT pathway was frequently mutated, with alterations in STAT5B, JAK1, JAK3, STAT3, and SOCS1.
  • Mutations in KRAS, TP53, and TERT were also identified, with overlapping profiles between Type I and Type II EATL.

Conclusions:

  • This study provides the most comprehensive genetic portrait of EATL to date.
  • SETD2 loss plays a significant role in T cell development and EATL lymphomagenesis.
  • The findings may inform future EATL classification and therapeutic strategies.

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