PRDM10-rearranged Soft Tissue Tumor

Puls, Florian; Pillay, Nischalan; Fagman, Henrik; Palin-Masreliez, Anne; Amary, Fernanda; Hansson, Magnus; Kindblom, Lars Gunnar; McCulloch, Tom; Meligonis, George; Muc, Ronald; Rissler, Pehr; Sumathi, Vaiyapuri P.; Tirabosco, Roberto; Hofvander, Jakob; Magnusson, Linda; Nilsson, Jenny; Flanagan, Adrienne M.; Mertens, Fredrik

doi:10.1097/pas.0000000000001207

Cited by 39 publications

(38 citation statements)

References 36 publications

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“…9 Their findings suggest that superficial CD34 positive fibroblastic tumor is genetically heterogenous and further investigation of this entity is warranted. 9 A low-grade myxofibrosarcoma was excluded in the current tumor based on the age of the patient, the lack of characteristic curvilinear vasculature, and the wellcircumscribed nature of the lesion with strong diffuse CD34 positivity and focal keratin staining. MIFS occurs at acral sites, displays myxoid nodules and pseuodolipoblasts and is typically CD34 negative.…”

Section: Discussionmentioning

confidence: 99%

Superficial CD34 Positive Fibroblastic Tumour with Myxoid Stroma

2022

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Superficial CD34 positive fibroblastic tumor is a rare low-grade neoplasm of the skin and subcutis with indolent behavior. This entity has been included in the current World Health Organisation (WHO) classification of soft tissue tumors. Pathological diagnosis can be challenging due to significant morphological overlap with other entities and the large spectrum of CD34 positive tumors. We report a case in a twenty-five male which showed characteristic diagnostic features, but in addition showed myxoid stroma. The presence of myxoid stroma has not been previously emphasized in this entity and broadens the histologic differential diagnosis significantly to include myxoid soft tissue tumors. A subset of these tumors harbor PRDM10-rearrangements, but a defining molecular feature has not yet been described, highlighting the need for further molecular characterization of this potentially genetically heterogenous tumor. Awareness of this entity among surgeons and pathologists is important to prevent misclassification as an aggressive sarcoma and avoid over-treatment.

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Section: Discussionmentioning

confidence: 99%

Superficial CD34 Positive Fibroblastic Tumour with Myxoid Stroma

2022

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“…PRDM10 gene fusions with either MED12 or CITED2 have been reported in a small proportion of undifferentiated pleomorphic sarcomas. These tumors have a relatively benign course, a distinct expression pattern and no or limited other mutations or numerical chromosomal aberrations ( 55 , 56 ). PRDM10 increases B-cell lymphoma-2 (Bcl-2) expression in vitro ( 57 ).…”

Section: Discussionmentioning

confidence: 99%

PRDM10directsFLCNexpression in a novel disorder overlapping with Birt–Hogg–Dubé syndrome and familial lipomatosis

Beek

Glykofridis

Oosterwijk

et al. 2022

Human Molecular Genetics

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Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder characterized by fibrofolliculomas, pulmonary cysts, pneumothoraces and renal cell carcinomas. Here, we reveal a novel hereditary disorder in a family with skin and mucosal lesions, extensive lipomatosis and renal cell carcinomas. The proband was initially diagnosed with BHD based on the presence of fibrofolliculomas, but no pathogenic germline variant was detected in FLCN, the gene associated with BHD. By whole exome sequencing we identified a heterozygous missense variant (p.(Cys677Tyr)) in a zinc-finger encoding domain of the PRDM10 gene which co-segregated with the phenotype in the family. We show that PRDM10Cys677Tyr loses affinity for a regulatory binding motif in the FLCN promoter, abrogating cellular FLCN mRNA and protein levels. Overexpressing inducible PRDM10Cys677Tyr in renal epithelial cells altered the transcription of multiple genes, showing overlap but also differences with the effects of knocking out FLCN. We propose that PRDM10 controls an extensive gene program and acts as a critical regulator of FLCN gene transcription in human cells. The germline variant PRDM10Cys677Tyr curtails cellular folliculin expression and underlies a distinguishable syndrome characterized by extensive lipomatosis, fibrofolliculomas and renal cell carcinomas.

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“…Using RNA-seq and other methodologies, analysis of 84 soft tissue sarcomas revealed that a significant subset of low-grade undifferentiated pleomorphic sarcoma (UPS) showed a gene fusion of PRDM10 either with MED12 or CITED2, suggesting that these rearrangements were specific for this less aggressive UPS subset [161]. Moreover, PRDM10-rearranged soft tissue tumors are characterized by pleomorphism and a low mitotic count [162]. Currently studies using integrated bioinformatics and network analysis have also recognized the role of PRDM10 in the onset, progression, and drug resistance of many malignancies, such as hepatocellular, prostate, and nasopharyngeal carcinoma, as well as gastric and rectum cancers [163][164][165][166][167][168]; although in our previous TGCA analysis, PRDM10 was either mutated or overexpressed in certain cancer types [45].…”

Section: Prdm10mentioning

confidence: 99%

Multifaceted Role of PRDM Proteins in Human Cancer

Casamassimi

Rienzo

Zazzo

et al. 2020

IJMS

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The PR/SET domain family (PRDM) comprise a family of genes whose protein products share a conserved N-terminal PR [PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1)] homologous domain structurally and functionally similar to the catalytic SET [Su(var)3-9, enhancer-of-zeste and trithorax] domain of histone methyltransferases (HMTs). These genes are involved in epigenetic regulation of gene expression through their intrinsic HMTase activity or via interactions with other chromatin modifying enzymes. In this way they control a broad spectrum of biological processes, including proliferation and differentiation control, cell cycle progression, and maintenance of immune cell homeostasis. In cancer, tumor-specific dysfunctions of PRDM genes alter their expression by genetic and/or epigenetic modifications. A common characteristic of most PRDM genes is to encode for two main molecular variants with or without the PR domain. They are generated by either alternative splicing or alternative use of different promoters and play opposite roles, particularly in cancer where their imbalance can be often observed. In this scenario, PRDM proteins are involved in cancer onset, invasion, and metastasis and their altered expression is related to poor prognosis and clinical outcome. These functions strongly suggest their potential use in cancer management as diagnostic or prognostic tools and as new targets of therapeutic intervention.

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PRDM10-rearranged Soft Tissue Tumor

Cited by 39 publications

References 36 publications

Superficial CD34 Positive Fibroblastic Tumour with Myxoid Stroma

Superficial CD34 Positive Fibroblastic Tumour with Myxoid Stroma

PRDM10directsFLCNexpression in a novel disorder overlapping with Birt–Hogg–Dubé syndrome and familial lipomatosis

Multifaceted Role of PRDM Proteins in Human Cancer

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