Chronological genome and single-cell transcriptome integration characterizes the evolutionary process of adult T cell leukemia-lymphoma

Makoto Yamagishi, Miyuki Kubokawa, Yuta Kuze, Ayako Suzuki, Akari Yokomizo, Seiichiro Kobayashi, Makoto Nakashima, Junya Makiyama, Masako Iwanaga, Takahiro Fukuda, Toshiki Watanabe, Yutaka Suzuki () and Kaoru Uchimaru ()
Additional contact information
Makoto Yamagishi: The University of Tokyo
Miyuki Kubokawa: The University of Tokyo
Yuta Kuze: The University of Tokyo
Ayako Suzuki: The University of Tokyo
Akari Yokomizo: The University of Tokyo
Seiichiro Kobayashi: Kanto Rosai Hospital
Makoto Nakashima: The University of Tokyo
Junya Makiyama: Sasebo City General Hospital
Masako Iwanaga: Nagasaki University Graduate School of Biomedical Sciences
Takahiro Fukuda: National Cancer Center Hospital
Toshiki Watanabe: St. Marianna University
Yutaka Suzuki: The University of Tokyo
Kaoru Uchimaru: The University of Tokyo

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25101-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25101-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25101-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().