Novel somatic alterations in unicentric and idiopathic multicentric Castleman disease. Eur J Haematol 2021 Dec;107(6):642-649
Date
08/26/2021Pubmed ID
34431136Pubmed Central ID
PMC9624446DOI
10.1111/ejh.13702Scopus ID
2-s2.0-85115257192 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
OBJECTIVES: Castleman disease (CD) is a heterogeneous group of disorders involving systemic inflammation and lymphoproliferation. Recently, clonal mutations have been identified in unicentric 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.
Author List
Goodman AM, Jeong AR, Phillips A, Wang HY, Sokol ES, Cohen PR, Sicklick J, Fajgenbaum DC, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultCastleman Disease
Chromosome Aberrations
Female
Humans
Karyotyping
Male
Middle Aged
Mutation
