Interleukin 1 receptor-associated kinase 1 (IRAK1) mutation is a common, essential driver for Kaposi sarcoma herpesvirus lymphoma

Yang, Dongmei; Chen, Wuguo; Xiong, Jessie; Sherrod, Carly J.; Henry, David H.; Dittmer, Dirk P.

doi:10.1073/pnas.1405423111

Cited by 36 publications

(43 citation statements)

References 39 publications

(36 reference statements)

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“…RHOA and CCND3 are dysregulated by Human T lymphotropic virus type I (HTLV-I) (61). For the DNA tumor viruses, KSV tumors appear to be driven by viral programming in immunocompromised settings with only a few described driver mutations including interleukin 1 receptor-associated kinase ( IRAK1 ) in primary effusion lymphoma (62). In HPV-associated squamous cell cervical carcinoma the most common driver mutations are PIK3CA, EP300, TP53, FBXW7 , and MAPK1 (63).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Transcriptome and Mutational Profiling of Endemic Burkitt Lymphoma Reveals EBV Type–Specific Differences

Kaymaz

Oduor

et al. 2017

Molecular Cancer Research

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Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in malaria-endemic equatorial Africa and nearly always contains Epstein-Barr virus (EBV), unlike sporadic Burkitt Lymphoma (sBL) that occurs with a lower incidence in developed countries. Given these differences and the variable clinical presentation and outcomes, we sought to further understand pathogenesis by investigating transcriptomes using RNA sequencing (RNAseq) from multiple primary eBL tumors compared to sBL tumors. Within eBL tumors, minimal expression differences were found based on: anatomical presentation site, in-hospital survival rates, and EBV genome type; suggesting that eBL tumors are homogeneous without marked subtypes. The outstanding difference detected using surrogate variable analysis was the significantly decreased expression of key genes in the immunoproteasome complex (PSMB9/β1i, PSMB10/β2i, PSMB8/β5i, and PSME2/PA28β) in eBL tumors carrying type 2 EBV compared to type 1 EBV. Secondly, in comparison to previously published pediatric sBL specimens, the majority of the expression and pathway differences was related to the PTEN/PI3K/mTOR signaling pathway and was correlated most strongly with EBV status rather than geographic designation. Third, common mutations were observed significantly less frequently in eBL tumors harboring EBV type 1, with mutation frequencies similar between tumors with EBV type 2 and without EBV. In addition to the previously reported genes, a set of new genes mutated in BL including TFAP4, MSH6, PRRC2C, BCL7A, FOXO1, PLCG2, PRKDC, RAD50, and RPRD2 were identified. Overall, these data establish that EBV, particularly EBV type 1, supports BL oncogenesis alleviating the need for certain driver mutations in the human genome.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Transcriptome and Mutational Profiling of Endemic Burkitt Lymphoma Reveals EBV Type–Specific Differences

Kaymaz

Oduor

et al. 2017

Molecular Cancer Research

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“…The upregulation of IRAK1 may cause an increased level of IRAK1 expression in HCC, as confirmed by our results. As for the missense mutation of IRAK1, a Phe196Ser change in IRAK1 was detected in primary effusion lymphoma (PEL),31 which caused the constitutive phosphorylation of IRAK1 in PEL and promoted the progression of PEL. We postulated that the specific missense mutation of IRAK1 existed in HCC to facilitate the development of IRAK1 via the phosphorylation of IRAK1.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and prognostic roles of IRAK1 in hepatocellular carcinoma tissues: an analysis of immunohistochemistry and RNA-sequencing data from the cancer genome atlas

Ye¹,

Gao²,

Wen³

et al. 2017

OTT

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BackgroundIRAK1 has been repoted to play an essential role in the development of multiple cancers. However, the clinical significance of IRAK1 in hepatocellular carcinoma (HCC) and the underlying molecular mechanism remain unclear. Therefore, we aimed to investigate the role of IRAK1 in the pathogenesis of HCC in this study.Materials and methodsHCC tissues and para-carcinoma tissues were collected for immunohistochemistry (IHC) analysis to evaluate IRAK1 expression. Data of IRAK1 expression were downloaded from the cancer genome atlas (TCGA) for analyzing the clinical significance of IRAK1. Receiver operating characteristic (ROC) curve and survival analyses were carried out to assess the diagnostic and prognostic significance of IRAK1 in IHC and TCGA data. Additionally, we investigated the alteration of IRAK1 gene in HCC from cBioPortal to generate a network of the interaction between IRAK1 and the neighboring genes. The influence of IRAK1 gene alteration on the prognosis of HCC patients was evaluated by survival analysis.ResultsAnalysis of both IHC and TCGA data revealed a significant upregulation of IRAK1 in HCC tissues. The IHC analysis revealed there was an increasing trend in IRAK1 expression among normal liver tissues, liver cirrhosis tissues, para-carcinoma tissues and HCC tissues. The ROC curves for IHC and TCGA data demonstrated that IRAK1 exhibited a significant diagnostic value for HCC. Moreover, IRAK1 expression was observed to be associated with tumor size, metastasis and T-stage. The survival analysis indicated that the upregulation of IRAK1 predicted a worse overall survival of HCC. Additionally, data from cBioPortal confirmed that 29% of HCC tissues possessed an alteration of the IRAK1 gene.ConclusionIRAK1 may act as an oncogene in the development of HCC with its overexpression in HCC. Moreover, IRAK1 might serve as a promising diagnostic and therapeutic target for HCC.

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“…Rather, the KSHV viral protein LANA drives MYC overexpression (143,144). Comparative genome hybridization uncovered fragile histidine triad (FHIT) deletion as overrepresented in PELs, and targeted sequencing studies identified a polymorphism in IL-1 receptor-associated kinase 1 (IRAK1) as significantly overrepresented in PELs (145,146). Moreover, IRAK1 signaling is required for PEL growth.…”

Section: Genomic Explorations Of Ks and Pelmentioning

confidence: 99%

Kaposi sarcoma–associated herpesvirus: immunobiology, oncogenesis, and therapy

Dittmer

Damania

2016

Journal of Clinical Investigation

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Interleukin 1 receptor-associated kinase 1 (IRAK1) mutation is a common, essential driver for Kaposi sarcoma herpesvirus lymphoma

Cited by 36 publications

References 39 publications

Comprehensive Transcriptome and Mutational Profiling of Endemic Burkitt Lymphoma Reveals EBV Type–Specific Differences

Comprehensive Transcriptome and Mutational Profiling of Endemic Burkitt Lymphoma Reveals EBV Type–Specific Differences

Diagnostic and prognostic roles of IRAK1 in hepatocellular carcinoma tissues: an analysis of immunohistochemistry and RNA-sequencing data from the cancer genome atlas

Kaposi sarcoma–associated herpesvirus: immunobiology, oncogenesis, and therapy

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