title: Interleukin 1 receptor-associated kinase 1 (IRAK1) mutation is a common, essential driver for Kaposi sarcoma herpesvirus lymphoma.
abstract: Primary effusion lymphoma (PEL) is an AIDS-defining cancer. All PELs carry Kaposi sarcoma-associated herpesvirus (KSHV). X chromosome-targeted sequencing of PEL identified 34 common missense mutations in 100% of cases. This included a Phe196Ser change in the interleukin 1 receptor-associated kinase 1 (IRAK1). The mutation was verified in primary PEL exudates. IRAK1 is the binding partner of MyD88, which is mutated in a fraction of Waldenström macroglobulinemia. Together, these two mediate toll-like receptor (TLR) signaling. IRAK1 was constitutively phosphorylated in PEL and required for survival, implicating IRAK1 and TLR signaling as a driver pathway in PEL and as a new drug development target.
authors.affiliation: Department of Microbiology and Immunology and Program in Global Oncology of the Lineberger Comprehensive Cancer Center, School of Medicine, and.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Immunology and Program in Global Oncology of the Lineberger Comprehensive Cancer Center, School of Medicine, and.
authors.forename: Wuguo
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Statistics and Operations Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; and.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of Microbiology and Immunology and Program in Global Oncology of the Lineberger Comprehensive Cancer Center, School of Medicine, and.
authors.forename: Carly J
authors.initials: CJ
authors.lastname: Sherrod
authors.affiliation: Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: David H
authors.initials: DH
authors.lastname: Henry
authors.affiliation: Department of Microbiology and Immunology and Program in Global Oncology of the Lineberger Comprehensive Cancer Center, School of Medicine, and ddittmer@med.unc.edu.
authors.forename: Dirk P
authors.initials: DP
authors.lastname: Dittmer
mesh_terms: D045744:Cell Line, Tumor; D006566:Herpesviridae Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019288:Herpesvirus 8, Human; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D054685:Lymphoma, Primary Effusion / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D009363:Neoplasm Proteins; D051193:Toll-Like Receptors; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases
keywords: IRAK; Kaposi sarcoma; herpesviruses; myd88; primary effusion lymphoma