Whole-genome sequencing facilitates patient-specific quantitative PCR-based minimal residual disease monitoring in acute lymphoblastic leukaemia, neuroblastoma and Ewing sarcoma.
Br J Cancer
; 126(3): 482-491, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-34471258
ABSTRACT
BACKGROUND:
Minimal residual disease (MRD) measurement is a cornerstone of contemporary acute lymphoblastic leukaemia (ALL) treatment. The presence of immunoglobulin (Ig) and T cell receptor (TCR) gene recombinations in leukaemic clones allows widespread use of patient-specific, DNA-based MRD assays. In contrast, paediatric solid tumour MRD remains experimental and has focussed on generic assays targeting tumour-specific messenger RNA, methylated DNA or microRNA.METHODS:
We examined the feasibility of using whole-genome sequencing (WGS) data to design tumour-specific polymerase chain reaction (PCR)-based MRD tests (WGS-MRD) in 18 children with high-risk relapsed cancer, including ALL, high-risk neuroblastoma (HR-NB) and Ewing sarcoma (EWS) (n = 6 each).RESULTS:
Sensitive WGS-MRD assays were generated for each patient and allowed quantitation of 1 tumour cell per 10-4 (0.01%)-10-5 (0.001%) mononuclear cells. In ALL, WGS-MRD and Ig/TCR-MRD were highly concordant. WGS-MRD assays also showed good concordance between quantitative PCR and droplet digital PCR formats. In serial clinical samples, WGS-MRD correlated with disease course. In solid tumours, WGS-MRD assays were more sensitive than RNA-MRD assays.CONCLUSIONS:
WGS facilitated the development of patient-specific MRD tests in ALL, HR-NB and EWS with potential clinical utility in monitoring treatment response. WGS data could be used to design patient-specific MRD assays in a broad range of tumours.
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Base de dados:
MEDLINE
Assunto principal:
Sarcoma de Ewing
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Rearranjo Gênico
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Biomarcadores Tumorais
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Neoplasia Residual
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Sequenciamento Completo do Genoma
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Neuroblastoma
Limite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Austrália