Chronological genome and single-cell transcriptome integration characterizes the evolutionary process of adult T cell leukemia-lymphoma.
Adult
Cell Line, Tumor
Cell Proliferation
/ genetics
Cells, Cultured
Clonal Evolution
/ genetics
Clone Cells
/ metabolism
Genome, Viral
/ genetics
HTLV-I Infections
/ virology
Human T-lymphotropic virus 1
/ genetics
Humans
Jurkat Cells
Leukemia-Lymphoma, Adult T-Cell
/ genetics
Mutation
RNA-Seq
/ methods
Receptor, Notch1
/ genetics
Receptors, Antigen, T-Cell
/ genetics
STAT3 Transcription Factor
/ genetics
Single-Cell Analysis
/ methods
Transcriptome
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 08 2021
10 08 2021
Historique:
received:
27
07
2020
accepted:
23
07
2021
entrez:
11
8
2021
pubmed:
12
8
2021
medline:
24
8
2021
Statut:
epublish
Résumé
Subclonal genetic heterogeneity and their diverse gene expression impose serious problems in understanding the behavior of cancers and contemplating therapeutic strategies. Here we develop and utilize a capture-based sequencing panel, which covers host hotspot genes and the full-length genome of human T-cell leukemia virus type-1 (HTLV-1), to investigate the clonal architecture of adult T-cell leukemia-lymphoma (ATL). For chronologically collected specimens from patients with ATL or pre-onset individuals, we integrate deep DNA sequencing and single-cell RNA sequencing to detect the somatic mutations and virus directly and characterize the transcriptional readouts in respective subclones. Characteristic genomic and transcriptomic patterns are associated with subclonal expansion and switches during the clinical timeline. Multistep mutations in the T-cell receptor (TCR), STAT3, and NOTCH pathways establish clone-specific transcriptomic abnormalities and further accelerate their proliferative potential to develop highly malignant clones, leading to disease onset and progression. Early detection and characterization of newly expanded subclones through the integrative analytical platform will be valuable for the development of an in-depth understanding of this disease.
Identifiants
pubmed: 34376672
doi: 10.1038/s41467-021-25101-9
pii: 10.1038/s41467-021-25101-9
pmc: PMC8355240
doi:
Substances chimiques
Receptor, Notch1
0
Receptors, Antigen, T-Cell
0
STAT3 Transcription Factor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4821Informations de copyright
© 2021. The Author(s).
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