Exome sequencing identifies recurrent BCOR alterations and the absence of KLF2, TNFAIP3 and MYD88 mutations in splenic diffuse red pulp small B-cell lymphoma.

Laurent Jallades (1, 2) , Lucile Baseggio (1, 2) , Pierre Sujobert (1, 2) , Sarah Huet (2, 1) , Kaddour Chabane (1, 2) , Evelyne Callet-Bauchu (1, 2) , Aurélie Verney (1) , Sandrine Hayette (2, 1) , Jean-Pierre Desvignes (3) , David Salgado (3) , Nicolas Lévy (4, 3) , Christophe Béroud (3) , Pascale Felman (1, 2) , Françoise Berger (2) , Jean-Pierre Magaud (1, 2) , Laurent Genestier (2) , Gilles Salles (5, 2) , Alexandra Traverse-Glehen (6)

1 Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL]
2 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
3 GMGF - Génétique Médicale et Génomique Fonctionnelle
4 TIMONE - Hôpital de la Timone [CHU - APHM]
5 Service d'hématologie [Hôpital Edouard Herriot - HCL]
6 Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud

Splenic diffuse red pulp lymphoma is an indolent small B-cell lymphoma recognised as a provisional entity in the WHO 2008 classification. Its precise relationship with other related splenic B-cell lymphomas with frequent leukaemic involvement or other lymphoproliferative disorders remains undetermined. We performed whole-exome sequencing to explore the genetic landscape of 10 splenic diffuse red pulp lymphoma cases from paired tumour and normal samples. A selection of 109 somatic mutations was then evaluated in a cohort including 42 splenic diffuse red pulp lymphoma samples and compared to those identified in 46 splenic marginal zone lymphoma and 8 hairy-cell leukaemia samples. Recurrent mutations or losses in BCOR (gene encoding the BCL6 corepressor)-frameshift (n=3), nonsense (n=2), splicing site (n=1), and copy number loss (n=4)- were identified in 10/42 splenic diffuse red pulp lymphoma (24%), whereas only one frameshift mutation was identified in 46 splenic marginal zone lymphoma cases (2%). Inversely, KLF2, TNFAIP3 and MYD88 mutations were rare (one KLF2 mutant out of 42 samples; 2%) or absent (TNFAIP3 and MYD88) in splenic diffuse red pulp lymphoma compared to splenic marginal zone lymphoma. These findings define an original genetic profile of splenic diffuse red pulp lymphoma, suggesting distinct mechanisms of pathogenesis from splenic marginal zone lymphoma and hairy-cell leukaemia.

Mots clés: Lymphoproliferative Disorders; Cytogenetics and Molecular Genetics; Indolent Non-Hodgkin's Lymphoma

Domaines: Cancer

Laurent Jallades, Lucile Baseggio, Pierre Sujobert, Sarah Huet, Kaddour Chabane, et al.. Exome sequencing identifies recurrent BCOR alterations and the absence of KLF2, TNFAIP3 and MYD88 mutations in splenic diffuse red pulp small B-cell lymphoma.. Haematologica, 2017, 102 (10), pp.1758 - 1766. ⟨10.3324/haematol.2016.160192⟩. ⟨hal-01583112⟩