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Single-cell sequencing reveals karyotype heterogeneity in murine and human malignancies.

Abstract：

BACKGROUND:Chromosome instability leads to aneuploidy, a state in which cells have abnormal numbers of chromosomes, and is found in two out of three cancers. In a chromosomal instable p53 deficient mouse model with accelerated lymphomagenesis, we previously observed whole chromosome copy number changes affecting all lymphoma cells. This suggests that chromosome instability is somehow suppressed in the aneuploid lymphomas or that selection for frequently lost/gained chromosomes out-competes the CIN-imposed mis-segregation. RESULTS:To distinguish between these explanations and to examine karyotype dynamics in chromosome instable lymphoma, we use a newly developed single-cell whole genome sequencing (scWGS) platform that provides a complete and unbiased overview of copy number variations (CNV) in individual cells. To analyse these scWGS data, we develop AneuFinder, which allows annotation of copy number changes in a fully automated fashion and quantification of CNV heterogeneity between cells. Single-cell sequencing and AneuFinder analysis reveals high levels of copy number heterogeneity in chromosome instability-driven murine T-cell lymphoma samples, indicating ongoing chromosome instability. Application of this technology to human B cell leukaemias reveals different levels of karyotype heterogeneity in these cancers. CONCLUSION:Our data show that even though aneuploid tumours select for particular and recurring chromosome combinations, single-cell analysis using AneuFinder reveals copy number heterogeneity. This suggests ongoing chromosome instability that other platforms fail to detect. As chromosome instability might drive tumour evolution, karyotype analysis using single-cell sequencing technology could become an essential tool for cancer treatment stratification.

journal_name

Genome Biol

journal_title

Genome biology

authors

Bakker B,Taudt A,Belderbos ME,Porubsky D,Spierings DC,de Jong TV,Halsema N,Kazemier HG,Hoekstra-Wakker K,Bradley A,de Bont ES,van den Berg A,Guryev V,Lansdorp PM,Colomé-Tatché M,Foijer F

doi

10.1186/s13059-016-0971-7

subject

Has Abstract

pub_date

2016-05-31 00:00:00

pages

115

issue

eissn

1474-7596

issn

1474-760X

pii

10.1186/s13059-016-0971-7

journal_volume

pub_type

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Single-cell sequencing reveals karyotype heterogeneity in murine and human malignancies.