Whole-genome sequencing facilitates patient-specific quantitative PCR-based minimal residual disease monitoring in acute lymphoblastic leukaemia, neuroblastoma and Ewing sarcoma

Autor: Marie Wong, Michelle J. Henderson, Caroline Atkinson, Glenn M. Marshall, Nicola C. Venn, Pooja Venkat, Michelle Haber, Alvin Kamili, Vinod Vijay Subhash, Vanessa Tyrrell, Murray D. Norris, Mark J. Cowley, Paul G Ekert, Dan Chen, Chelsea Mayoh, Rosemary Sutton, Toby Trahair, Jamie I. Fletcher, Libby Huang
Rok vydání: 2021
Předmět:
Zdroj: British Journal of Cancer. 126:482-491
ISSN: 1532-1827
0007-0920
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: