Polymorphism of the CD30 Promoter Microsatellite Repressive Element Is Associated with Development of Primary Cutaneous Lymphoproliferative Disorders

Franchina, Maria; Kadin, Marshall E.; Abraham, Lawrence J.

doi:10.1158/1055-9965.epi-04-0826

Cited by 16 publications

(11 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Perhaps genetic polymorphism of an immune response gene is an important factor. 69,70 Because the atypical cells of LyP-A have been reported to express Th2-associated markers CD30 and CCR4 71,72 and because messenger RNA for one or more Th2 cytokines is expressed in LyP-A infiltrates, 73 it is plausible that neutrophils and/or eosinophils are recruited into the dermal infiltrate in LyP-A by cytokines secreted by activated type A cells, whereas the atypical cerebriform lymphocytes of LyP-B may be low producers of Th2 cytokines. 74 The spontaneous disappearance of CD30+ cells in LyP-A lesions may be self-regulated by transforming growth factor-b secreted by the preneoplastic cells themselves, whereas cell-mediated host response against the preneoplastic cells is muted in a Th2-predominant microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Lymphomatoid Papulosis Followed by Pityriasis Lichenoides: A Common Pathogenesis?

Vonderheid¹,

Kadin²,

Gocke³

2011

The American Journal of Dermatopathology

View full text Add to dashboard Cite

Pityriasis lichenoides (PL) and lymphomatoid papulosis (LyP) are uncommon idiopathic eruptions with overlapping clinical and histological features. Although current opinion indicates that PL and LyP are distinct and separate entities, molecular genetic evidence of T-cell clonality in both conditions suggests that an etiopathogenic relationship may exist. We report a patient who was diagnosed with LyP type B in 1985 followed by PL after 11 years. We hypothesize that LyP followed by PL in the same patient reflects differences in the host immune response to a common antigenic stimulus.

show abstract

Section: Discussionmentioning

confidence: 99%

Lymphomatoid Papulosis Followed by Pityriasis Lichenoides: A Common Pathogenesis?

Vonderheid¹,

Kadin²,

Gocke³

2011

The American Journal of Dermatopathology

View full text Add to dashboard Cite

show abstract

“…In the regulatory region, polymorphic STRs in the FLI1, ECE-1c and CD30 gene promoters have been associated with lupus [31], Alzheimer’s disease [32] and primary cutaneous lymphoproliferative disorders [33], respectively.…”

Section: Introductionmentioning

confidence: 99%

STaRRRT: a table of short tandem repeats in regulatory regions of the human genome

et al. 2013

View full text Add to dashboard Cite

BackgroundTandem repeats (TRs) are unstable regions commonly found within genomes that have consequences for evolution and disease. In humans, polymorphic TRs are known to cause neurodegenerative and neuromuscular disorders as well as being associated with complex diseases such as diabetes and cancer. If present in upstream regulatory regions, TRs can modify chromatin structure and affect transcription; resulting in altered gene expression and protein abundance. The most common TRs are short tandem repeats (STRs), or microsatellites. Promoter located STRs are considerably more polymorphic than coding region STRs. As such, they may be a common driver of phenotypic variation. To study STRs located in regulatory regions, we have performed genome-wide analysis to identify all STRs present in a region that is 2 kilobases upstream and 1 kilobase downstream of the transcription start sites of genes.ResultsThe Short Tandem Repeats in Regulatory Regions Table, STaRRRT, contains the results of the genome-wide analysis, outlining the characteristics of 5,264 STRs present in the upstream regulatory region of 4,441 human genes. Gene set enrichment analysis has revealed significant enrichment for STRs in cellular, transcriptional and neurological system gene promoters and genes important in ion and calcium homeostasis. The set of enriched terms has broad similarity to that seen in coding regions, suggesting that regulatory region STRs are subject to similar evolutionary pressures as STRs in coding regions and may, like coding region STRs, have an important role in controlling gene expression.ConclusionsSTaRRRT is a readily-searchable resource for investigating potentially polymorphic STRs that could influence the expression of any gene of interest. The processes and genes enriched for regulatory region STRs provide potential novel targets for diagnosing and treating disease, and support a role for these STRs in the evolution of the human genome.

show abstract

“…Our in vitro experiments support Meq’s previously demonstrated transcriptional regulation of CD30 [18], and, also show that the transcriptional profile generally follows genetic resistance and susceptibility to MD. A similar phenomenon has been observed in the CD30 over-expressing human cutaneous lymphoproliferative disease lymphomatoid papulosis [4,125]: allelic differences in the CD30 transcription are due to polymorphisms in the human CD30 microsatellite repressor element (located −1.2 kb and −336 bp of the CD30 promoter) and are associated with disease progression to lymphoma [125]. …”

Section: Discussionmentioning

confidence: 54%

Nuclear Factor kappa B is central to Marek’s Disease herpesvirus induced neoplastic transformation of CD30 expressing lymphocytes in-vivo

Kumar

Kunec

Buza

et al. 2012

BMC Systems Biology

View full text Add to dashboard Cite

BackgroundMarek’s Disease (MD) is a hyperproliferative, lymphomatous, neoplastic disease of chickens caused by the oncogenic Gallid herpesvirus type 2 (GaHV-2; MDV). Like several human lymphomas the neoplastic MD lymphoma cells overexpress the CD30 antigen (CD30hi) and are in minority, while the non-neoplastic cells (CD30lo) form the majority of population. MD is a unique natural in-vivo model of human CD30hi lymphomas with both natural CD30hi lymphomagenesis and spontaneous regression. The exact mechanism of neoplastic transformation from CD30lo expressing phenotype to CD30hi expressing neoplastic phenotype is unknown. Here, using microarray, proteomics and Systems Biology modeling; we compare the global gene expression of CD30lo and CD30hi cells to identify key pathways of neoplastic transformation. We propose and test a specific mechanism of neoplastic transformation, and genetic resistance, involving the MDV oncogene Meq, host gene products of the Nuclear Factor Kappa B (NF-κB) family and CD30; we also identify a novel Meq protein interactome.ResultsOur results show that a) CD30lo lymphocytes are pre-neoplastic precursors and not merely reactive lymphocytes; b) multiple transformation mechanisms exist and are potentially controlled by Meq; c) Meq can drive a feed-forward cycle that induces CD30 transcription, increases CD30 signaling which activates NF-κB, and, in turn, increases Meq transcription; d) Meq transcriptional repression or activation of the CD30 promoter generally correlates with polymorphisms in the CD30 promoter distinguishing MD-lymphoma resistant and susceptible chicken genotypes e) MDV oncoprotein Meq interacts with proteins involved in physiological processes central to lymphomagenesis.ConclusionsIn the context of the MD lymphoma microenvironment (and potentially in other CD30hi lymphomas as well), our results show that the neoplastic transformation is a continuum and the non-neoplastic cells are actually pre-neoplastic precursor cells and not merely immune bystanders. We also show that NF-κB is a central player in MDV induced neoplastic transformation of CD30-expressing lymphocytes in vivo. Our results provide insights into molecular mechanisms of neoplastic transformation in MD specifically and also herpesvirus induced lymphoma in general.

show abstract

Polymorphism of the CD30 Promoter Microsatellite Repressive Element Is Associated with Development of Primary Cutaneous Lymphoproliferative Disorders

Cited by 16 publications

References 15 publications

Lymphomatoid Papulosis Followed by Pityriasis Lichenoides: A Common Pathogenesis?

Lymphomatoid Papulosis Followed by Pityriasis Lichenoides: A Common Pathogenesis?

STaRRRT: a table of short tandem repeats in regulatory regions of the human genome

Nuclear Factor kappa B is central to Marek’s Disease herpesvirus induced neoplastic transformation of CD30 expressing lymphocytes in-vivo

Contact Info

Product

Resources

About