Novel Somatic Alterations in Unicentric and Idiopathic Multicentric Castleman Disease
Autor: | Ethan Sokol, Philip R Cohen, Jason K. Sicklick, Razelle Kurzrock, Alexis Phillips, Huan-You Wang, David C. Fajgenbaum, Aaron M. Goodman, Ah-Reum Jeong |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Adult
Male Pathology medicine.medical_specialty Somatic cell Locus (genetics) medicine.disease_cause Article Biopsy Gene duplication medicine Humans Chromosome Aberrations Mutation medicine.diagnostic_test urogenital system business.industry Castleman disease Castleman Disease Hematology General Medicine Middle Aged medicine.disease Phenotype Karyotyping Immunohistochemistry Female business |
Zdroj: | Eur J Haematol |
Popis: | Objectives Castleman disease (CD) is a heterogeneous group of disorders involving systemic inflammation and lymphoproliferation. Recently, clonal mutations have been identified in unitcentric CD (UCD) and idiopathic multicentric CD (iMCD), suggesting a potential underlying neoplastic process. Methods Patients with UCD or iMCD with next generation sequencing (NGS) data on tissue DNA and/or circulating tumor DNA (ctDNA) were included. Results Five patients were included, 4 with iMCD and 1 with UCD. Four patients (80%) were women; median age was 40 years. Three of five patients (60%) had ≥1 clonal mutation detected on biopsy among the genes included in the panel. One patient with iMCD had a 14q32-1p35 rearrangement and a der(1)dup(1)(q42q21)del(1)(q42) (1q21 being IL-6R locus) on karyotype. This patient also had a NF1 K2459fs alteration on ctDNA (0.3%). Another patient with iMCD had a KDM5C Q836* mutation, and one patient with UCD had a TNS3-ALK fusion but no ALK expression by immunohistochemistry. Conclusions We report 4 novel somatic alterations found in patients with UCD or iMCD. The 1q21 locus contains IL-6R, and duplication of this locus may increase IL-6 expression. These findings suggest that a clonal process may be responsible for the inflammatory phenotype in some patients with UCD and iMCD. |
Databáze: | OpenAIRE |
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