Clonal Evolution and Changes in Two AML Patients Detected with A Novel Single-Cell DNA Sequencing Platform

Scientific Reports
Liwen XuJames Zehnder

Abstract

Next-generation sequencing (NGS) is used to detect gene variants in genetically complex cell populations of cancer patient samples. Traditional bulk analysis can only provide average variant allele frequencies of the targeted genes across all sampled cells. It fails to resolve mutational co-occurrences and may miss rare cancer cells. Genome analysis at the single cell level offers the opportunity to more fully resolve clonal architecture. Peripheral blood mononuclear cells were sampled from acute myeloid leukemia patients longitudinally and single-cell DNA sequencing libraries were generated with a novel droplet-based microfluidics approach. Molecular profiling of single nucleotide variants across thousands of cells revealed genetic chimerism in patients after bone marrow transplantation (BMT). Importantly, hierarchical clustering analysis of single nucleotide variants (SNVs) uncovered a distinct oncogenic clone of cells carrying mutated tumor-suppressor and/or oncogene(s). This novel single-cell DNA sequencing approach enabled precise monitoring of engraftment and revealed clonal evolution of oncogenic cells during the progression and treatment of the disease.

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Citations

Oct 22, 2020·Genome Biology·Elisa Ten HackenCatherine J Wu
Aug 23, 2020·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Robert Salomon, David Gallego-Ortega
Jan 12, 2021·Current Opinion in Hematology·Ilaria Iacobucci, Charles G Mullighan
Dec 6, 2020·Nature Reviews. Clinical Oncology·Satyen H GohilKenneth J Livak
Mar 27, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Xue BaiZhiwei Zhang
Jun 27, 2021·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Robert Salomon
Jun 29, 2021·Biomarker Research·Lamia MadaciRégis Costello
Jul 30, 2021·Frontiers in Immunology·Daniel BodeDavid G Kent
Oct 14, 2020·Analytical Chemistry·Iain C ClarkAdam R Abate

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Methods Mentioned

BETA
single-cell sequencing
DNA-seq
blood drawings

Software Mentioned

freebayes
R
DNAnexus
NextGENe
Tapestri Analysis
gplots
Mission
Rtsne

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