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Single-Cell DNA and RNA Sequencing over A 29-Year Period of A CLL Patient

ABSTRACT:

Chronic lymphocytic leukemia (CLL) is a frequent B-cell malignancy characterized by recurrent somatic chromosome alterations and a low level of point mutations. Here we present single nucleotide polymorphism (SNP) microarray analyses of a single CLL patient over 29-years of observation and treatment, and transcriptome and whole genome sequencing at selected timepoints. We identified chromosome alterations of 13q14-, 6q- and 12q+ in early cell clones, elimination of clonal populations following therapy, and subsequent appearance of a clone containing trisomy 12 and a chromosome 10 copy neutral loss of heterogeneity (LOH) that marks a major population dominant at death. Serial single cell RNA sequencing revealed elevated mRNA expression of the FOS, JUN and KLF4 genes just before the appearance of acute disease requiring therapy. This gene expression pattern became undetectable following therapy, but reoccurred following relapse. Transcriptome evolution indicates that complex expression changes occur over time. In conclusion, CLL can evolve gradually during indolent phases, and undergo rapid changes following therapy.

PROVIDER: phs001181 | dbGaP |

SECONDARY ACCESSION(S): PRJNA336364PRJNA336365

REPOSITORIES: dbGaP

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			Action	DRS
	GapExchange_phs001181.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	Study_Report.phs001181.CLL_MultipleCellClones.v1.p1.MULTI.pdf	Pdf
	manifest_phs001181.CLL_MultipleCellClones.v1.p1.c1.DS-CA-MDS.pdf	Pdf
	datadict_v2.xsl	Other

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