Interleukin 1 receptor-associated kinase 1 (IRAK1) mutation is a common, essential driver for Kaposi sarcoma herpesvirus lymphoma.
basic_science · Level V
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- Record sourced from PubMed, PMID 25341731.
- Also identified by DOI 10.1073/pnas.1405423111 and PMC identifier 4226132.
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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.
Medical subject headings
- Herpesviridae Infections
- Herpesvirus 8, Human
- Interleukin-1 Receptor-Associated Kinases
- Lymphoma, Primary Effusion
- Mutation
- Neoplasm Proteins
- Signal Transduction