A highly heterogeneous mutational pattern in POEMS syndrome.
Leukemia
; 35(4): 1100-1107, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33262528
ABSTRACT
POEMS syndrome is a rare plasma cell dyscrasia. Little is known about its pathogenesis and genetic features. We analyzed the mutational features of purified bone marrow plasma cells from 42 patients newly diagnosed with POEMS syndrome using a two-step strategy. Whole exome sequencing of ten patients showed a total of 170 somatic mutations in exonic regions and splicing sites, with paired peripheral blood mononuclear cells as a control. Three significantly mutated genes-LILRB1 (10%), HEATR9 (20%), and FMNL2 (10%)-and eight mutated known driver genes (MYD88, NFKB2, CHD4, SH2B3, POLE, STAT3, CHD3, and CUX1) were identified. Target region sequencing of 77 genes were then analyzed to validate the mutations in an additional 32 patients. A total of 32 mutated genes were identified, and genes recurrently mutated in more than three patients included CUX1 (19%), DNAH5 (16%), USH2A (16%), KMT2D (16%), and RYR1 (12%). Driver genes of multiple myeloma (BIRC3, LRP1B, KDM6A, and ATM) and eleven genes reported in light-chain amyloidosis were also identified in target region sequencing. Notably, VEGFA mutations were detected in one patient. Our study revealed heterogeneous genomic profiles of bone marrow plasma cells in POEMS syndrome, which might share some similarity to that of other plasma cell diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores
/
Síndrome POEMS
/
Heterogeneidade Genética
/
Predisposição Genética para Doença
/
Estudos de Associação Genética
/
Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Leukemia
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China