Genomic profiling in amyloid light-chain amyloidosis reveals mutation profiles associated with overall survival.
Amyloid
; 27(1): 36-44, 2020 Mar.
Article
en En
| MEDLINE
| ID: mdl-31635489
ABSTRACT
Background:
Amyloid light chain (AL) amyloidosis is characterized by tissue deposition of amyloid fibres derived from immunoglobulin that can lead to irreversible organ damage. Information about genomic profiles of AL amyloidosis is lacking.Methods:
In this study, we adopted a two-step strategy to investigate the mutational profile of AL amyloidosis bone marrow plasma cells (PCs) and their clinical implications. In step one, whole-exome sequencing was performed in bone marrow PCs and paired with normal tissue from 10 AL amyloidosis patients, by which we identified 10 significantly mutated genes (SMGs). In step two, we constituted a targeted gene sequencing (TGS) panel covering the frequently mutated genes identified in step one, genes reported in prior AL amyloidosis studies, and known cancer driver mutations. Then, we analysed an expanded cohort of AL amyloidosis patients (N = 48) with this panel comprising 98 genes.Results:
Four recurrent mutations were identified by TGS and verified by Sanger sequencing ASB15 (c. 844 C > T), ASCC3 (c. 1595 A > G), HIST1H1E (c. 311 C > T) and KRAS (c. 35 G > A), among which the first three mutations were associated with inferior overall survival (OS). Additionally, we found that the number of mutations identified by the TGS panel of 98 genes could be a prognostic predictor for OS.Conclusions:
In summary, we revealed genomic profiling in AL amyloidosis and found mutation profiles associated with OS.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Histonas
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Proteínas
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Proteínas Proto-Oncogénicas p21(ras)
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ADN Helicasas
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Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas
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Mutación
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Amyloid
Asunto de la revista:
BIOQUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China