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Mutational Landscape of Grey Zone Lymphoma

ABSTRACT: The mutational landscape of grey zone lymphoma (GZL) has not yet been established and differences to related entities are mostly unknown. Here, we studied coding sequence mutations of 50 EBV-negative GZL and 20 polymorphic EBV-positive DLBCL NOS (poly-EBV-L) in comparison to classical Hodgkin lymphoma (cHL), primary mediastinal B cell lymphoma (PMBCL), and diffuse large B cell lymphoma (DLBCL). Paired exomes of 21 GZL and 7 poly-EBV-L cases were analyzed as a discovery cohort followed by targeted sequencing of 217 genes in an extension cohort of 29 GZL and 13 poly-EBV-L cases. GZL cases with thymic niche involvement displayed a mutation profile closely resembling cHL and PMBCL, with SOCS1 (45%), B2M (45%), TNFAIP3 (35%), GNA13 (35%) and NFKBIA (29%) being the most recurrently mutated genes. In contrast, GZL cases without thymic niche involvement (N=18) had a significantly distinct pattern, enriched in mutations related to apoptosis defects (TP53 (39%), BCL2 (28%), BIRC6 (22%)) and depleted in GNA13, XPO1 or NFKB signaling pathway mutations (TNFAIP3, NFKBIE, IKBKB, NFKBIA). Poly-EBV-L cases presented a distinct mutational profile including STAT3, PRKDC mutations and a significantly lower coding-mutation load in comparison to EBV-negative GZL. Our study highlights characteristic mutational patterns in GZL associated with presentation in the thymic niche suggesting a common cell of origin and disease evolution with related anterior mediastinal lymphomas.

PROVIDER: EGAS00001004482 | EGA |

REPOSITORIES: EGA

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