Abstract:
:Measuring minimal residual disease in cancer has applications for prognosis, monitoring treatment and detection of recurrence. Simple sequence-based methods to detect nucleotide substitution variants have error rates (about 10-3) that limit sensitive detection. We developed and characterized the performance of MASQ (multiplex accurate sensitive quantitation), a method with an error rate below 10-6. MASQ counts variant templates accurately in the presence of millions of host genomes by using tags to identify each template and demanding consensus over multiple reads. Since the MASQ protocol multiplexes 50 target loci, we can both integrate signal from multiple variants and capture subclonal response to treatment. Compared to existing methods for variant detection, MASQ achieves an excellent combination of sensitivity, specificity and yield. We tested MASQ in a pilot study in acute myeloid leukemia (AML) patients who entered complete remission. We detect leukemic variants in the blood and bone marrow samples of all five patients, after induction therapy, at levels ranging from 10-2 to nearly 10-6. We observe evidence of sub-clonal structure and find higher target variant frequencies in patients who go on to relapse, demonstrating the potential for MASQ to quantify residual disease in AML.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Moffitt AB,Spector MS,Andrews P,Kendall J,Alexander J,Stepansky A,Ma B,Kolitz J,Chiorazzi N,Allen SL,Krasnitz A,Wigler M,Levy D,Wang Zdoi
10.1093/nar/gkaa090subject
Has Abstractpub_date
2020-04-17 00:00:00pages
e40issue
7eissn
0305-1048issn
1362-4962pii
5742832journal_volume
48pub_type
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