Details

Autor(en) / Beteiligte

• Roberti, Annalisa
• Dobay, Maria Pamela
• Bisig, Bettina
• Vallois, David
• Boéchat, Cloé
• Lanitis, Evripidis
• Bouchindhomme, Brigitte
• Parrens, Marie- Cécile
• Bossard, Céline
• Quintanilla-Martinez, Leticia
• Missiaglia, Edoardo
• Gaulard, Philippe
• de Leval, Laurence

Titel

Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations

Ist Teil von

• Nature communications, 2016-09, Vol.7 (1), p.12602-12602, Article 12602

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Enteropathy-associated T-cell lymphoma (EATL), a rare and aggressive intestinal malignancy of intraepithelial T lymphocytes, comprises two disease variants (EATL-I and EATL-II) differing in clinical characteristics and pathological features. Here we report findings derived from whole-exome sequencing of 15 EATL-II tumour-normal tissue pairs. The tumour suppressor gene SETD2 encoding a non-redundant H3K36-specific trimethyltransferase is altered in 14/15 cases (93%), mainly by loss-of-function mutations and/or loss of the corresponding locus (3p21.31). These alterations consistently correlate with defective H3K36 trimethylation. The JAK/STAT pathway comprises recurrent STAT5B (60%), JAK3 (46%) and SH2B3 (20%) mutations, including a STAT5B V712E activating variant. In addition, frequent mutations in TP53 , BRAF and KRAS are observed. Conversely, in EATL-I, no SETD2 , STAT5B or JAK3 mutations are found, and H3K36 trimethylation is preserved. This study describes SETD2 inactivation as EATL-II molecular hallmark, supports EATL-I and -II being two distinct entities, and defines potential new targets for therapeutic intervention. Enteropathy associated T-cell lymphoma -EATL- affects the intestine and there are two different subtypes. In this study, the authors carry out exome sequencing of the type II variant and find that it is characterized by recurrent mutations in the histone methyltransferase SETD2 that are accompanied by altered H3K6 methylation.