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Integrated Single-Cell Analysis in Chronic Lymphocytic Leukemia

ABSTRACT:

Intratumoral genetic heterogeneity has been characterized across cancers by genome sequencing of bulk tumors, including chronic lymphocytic leukemia (CLL). In order to more accurately identify subclones, define phylogenetic relationships, and probe genotype-phenotype relationships, we developed methods for targeted mutation detection in DNA and RNA isolated from thousands of single cells from five CLL samples. By clearly resolving phylogenic relationships, we uncovered mutated LCP1 and WNK1 as novel CLL drivers, supported by functional evidence demonstrating their impact on CLL pathways. Integrative analysis of somatic mutations with transcriptional states prompts the idea that convergent evolution generates phenotypically similar cells in distinct genetic branches, thus creating a cohesive expression profile in each CLL sample despite the presence of genetic heterogeneity. Our study highlights the potential for single-cell RNA-based targeted analysis to sensitively determine transcriptional and mutational profiles of individual cancer cells leading to increased understanding of driving events in malignancy.

Reprinted from Genome Research, with permission from Publisher.

PROVIDER: phs001372 | dbGaP |

SECONDARY ACCESSION(S): PRJNA387322PRJNA387321

REPOSITORIES: dbGaP

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			Action	DRS
	GapExchange_phs001372.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	Study_Report.phs001372.CLL_IntegratedSingleCell.v1.p1.MULTI.pdf	Pdf
	manifest_phs001372.CLL_IntegratedSingleCell.v1.p1.c1.GRU.pdf	Pdf
	datadict_v2.xsl	Other

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