Longitudinal Single-Cell Dynamics of Chromatin Accessibility and Mitochondrial Mutations in Chronic Lymphocytic Leukemia Mirror Disease History.

Cancer Discovery
Livius PenterCatherine J Wu

Abstract

While cancers evolve during disease progression and in response to therapy, temporal dynamics remain difficult to study in humans due to the lack of consistent barcodes marking individual clones in vivo. We employ mitochondrial single-cell assay for transposase-accessible chromatin with sequencing to profile 163,279 cells from 9 patients with chronic lymphocytic leukemia (CLL) collected across disease course and utilize mitochondrial DNA (mtDNA) mutations as natural genetic markers of cancer clones. We observe stable propagation of mtDNA mutations over years in the absence of strong selective pressure, indicating clonal persistence, but dramatic changes following tight bottlenecks, including disease transformation and relapse posttherapy, paralleled by acquisition of copy-number variants and changes in chromatin accessibility and gene expression. Furthermore, we link CLL subclones to distinct chromatin states, providing insight into nongenetic sources of relapse. mtDNA mutations thus mirror disease history and provide naturally occurring genetic barcodes to enable patient-specific study of cancer subclonal dynamics. SIGNIFICANCE: Single-cell multi-omic profiling of CLL reveals the utility of somatic mtDNA mutations as in vivo b...Continue Reading

References

May 5, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yohei KirinoTsutomu Suzuki
Feb 28, 2008·Cancer Immunology, Immunotherapy : CII·Frank GrünebachPeter Brossart
Apr 5, 2011·Cell·Alan AshworthJorge S Reis-Filho
Mar 30, 2013·Science·Mario L SuvàBradley E Bernstein
Dec 10, 2014·Current Protocols in Bioinformatics·Marie T LottDouglas C Wallace
Aug 19, 2015·Nature Reviews. Genetics·James B Stewart, Patrick F Chinnery
Oct 16, 2015·Nature·Dan A LandauCatherine J Wu
Mar 20, 2016·Proceedings of the National Academy of Sciences of the United States of America·Daniel J HodsonLouis M Staudt
Feb 12, 2017·Cell·Nicholas McGranahan, Charles Swanton
Feb 21, 2018·Trends in Cancer·Ravi Salgia, Prakash Kulkarni
Apr 26, 2018·Blood·Davide RossiGianluca Gaidano
May 31, 2019·Nature·Michaela GruberCatherine J Wu
Jun 11, 2019·Cell·Tim StuartRahul Satija
Jun 28, 2019·Blood·Anne QuinquenelUNKNOWN French Innovative Leukemia Organization (FILO) CLL Group
Oct 22, 2019·European Journal of Immunology·Andrea CossarizzaArturo Zychlinsky
Jan 8, 2020·Nature Methods·Chenxu ZhuBing Ren
Feb 7, 2020·Nature Genetics·Yuan YuanUNKNOWN PCAWG Consortium
Jul 30, 2020·The New England Journal of Medicine·Jan A Burger
Aug 14, 2020·Nature Biotechnology·Caleb A LareauVijay G Sankaran
Sep 18, 2020·Science Translational Medicine·Pavan BachireddyCatherine J Wu
Sep 30, 2020·Nature Reviews. Genetics·James B Stewart, Patrick F Chinnery
Oct 10, 2020·Nature Reviews. Cancer·Jean-Christophe MarineMark A Dawson
Feb 27, 2021·Nature Genetics·Jeffrey M GranjaWilliam J Greenleaf
Apr 10, 2021·Nature Metabolism·Alexander N GorelickEd Reznik

❮ Previous
Next ❯

Related Concepts

Related Feeds

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.