Low Mutational Burden of Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue in Patients with Primary Sjogren's Syndrome

Johanna A A Bult, Jessica R Plaça, Erlin A Haacke, M Martijn Terpstra, Gwenny M Verstappen, Frederik K L Spijkervet, Frans G M Kroese, Wouter J Plattel, Joost S P Vermaat, Hendrika Bootsma, Bert van der Vegt, Arjan Diepstra, Anke van den Berg, Klaas Kok, Marcel Nijland*

*Corresponding author for this work

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Patients with primary Sjogren's syndrome (pSS) are at risk of developing extranodal marginal zone lymphoma (ENMZL) of the mucosa-associated lymphoid tissue (MALT) in the parotid glands. Unlike recurrent genomic aberrations observed in MALT lymphoma, which were not associated with pSS (non-pSS), it is unknown which somatic aberrations underlie the development of pSS-associated MALT lymphomas. Whole-exome sequencing was performed on 17 pSS-associated MALT lymphomas. In total, 222 nonsynonymous somatic variants affecting 182 genes were identified across the 17 cases. The median number of variants was seven (range 2-78), including three cases with a relatively high mutational load (≥24/case). Out of 16 recurrently mutated genes, ID3, TBL1XR1, PAX5, IGLL5 and APC are known to be associated with lymphomagenesis. A total of 18 copy number alterations were detected in eight cases. MALT1 translocations were not detected. With respect to outcome, only two cases relapsed outside of the salivary glands. Both had a high mutational load, suggesting a more advanced stage of lymphoma. The low mutational load and lack of a clear lymphoma-related mutation profile suggests that localized pSS-associated MALT lymphomas are genomically more stable than non-pSS MALT lymphomas and most likely depend on a stimulatory micro-environment.

Original languageEnglish
Article number1010
Number of pages11
Issue number4
Publication statusPublished - 1-Feb-2022


  • extranodal marginal lymphoma of mucosa-associated lymphoid tissue
  • Sjogren's syndrome
  • whole-exome sequencing
  • mutational analysis

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