Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mutational landscape of grey zone lymphoma (GZL) has not yet been established and differences to related entities are largely 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 large B cell lymphoma (PMBCL), and diffuse large B cell lymphoma (DLBCL). Exomes of 21 GZL and 7 poly-EBV-L cases along with paired normals 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 (anterior mediastinal mass) displayed a mutation profile closely resembling cHL and PMBCL, with SOCS1 (45%), B2M (45%), TNFAIP3 (35%), GNA13 (35%), LRRN3 (32%) 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, XPO1or NFKB signaling pathway mutations (TNFAIP3, NFKBIE, IKBKB, NFKBIA). They also presented more BCL2/BCL6 rearrangements as opposed to thymic GZL. Poly-EBV-L cases presented a distinct mutational profile including STAT3 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 with disease evolution overlapping with related anterior mediastinal lymphomas.
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PMID:Mutational Landscape of Grey Zone Lymphoma. 3296 52

Plasmablastic lymphoma (PBL) is a rare and clinically aggressive neoplasm that typically occurs in immunocompromised individuals, including those with HIV infection and solid organ allograft recipients. Most prior studies have focused on delineating the clinicopathologic features and genetic attributes of HIV-related PBLs, where MYC deregulation and EBV infection, and more recently, mutations in JAK/STAT, MAP kinase, and NOTCH pathway genes have been implicated in disease pathogenesis. The phenotypic spectrum of post-transplant (PT)-PBLs is not well characterized and data on underlying genetic alterations are limited. Hence, we performed comprehensive histopathologic and immunophenotypic evaluation and targeted sequencing of 18 samples from 11 patients (8 males, 3 females, age range 12-76 years) with PT-PBL; 8 de novo and 3 preceded by other types of PTLDs. PT-PBLs displayed morphologic and immunophenotypic heterogeneity and some features overlapped those of plasmablastic myeloma. Six (55%) cases were EBV+ and 5 (45%) showed MYC rearrangement by fluorescence in situ hybridization. Recurrent mutations in epigenetic regulators (KMT2/MLL family, TET2) and DNA damage repair and response (TP53, mismatch repair genes, FANCA, ATRX), MAP kinase (KRAS, NRAS, HRAS, BRAF), JAK/STAT (STAT3, STAT6, SOCS1), NOTCH (NOTCH1, NOTCH3, SPEN), and immune surveillance (FAS, CD58) pathway genes were observed, with EBV+ and EBV- cases exhibiting similarities and differences in their mutational profiles. Clinical outcomes also varied, with survival ranging from 0-15.9 years postdiagnosis. Besides uncovering the biological heterogeneity of PT-PBL, our study highlights similarities and distinctions between PT-PBLs and PBLs occurring in other settings and reveals potentially targetable oncogenic pathways in disease subsets.
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PMID:Phenogenomic heterogeneity of post-transplant plasmablastic lymphomas. 3329 69


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