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

Autor: Tristan V. de Jong, Maria Colomé-Tatché, Diana C.J. Spierings, David Porubsky, Nancy Halsema, Mirjam E. Belderbos, Allan Bradley, Victor Guryev, Peter M. Lansdorp, Eveline S. J. M. de Bont, Hinke G. Kazemier, Floris Foijer, Aaron Taudt, Karina Hoekstra-Wakker, Anke van den Berg, Bjorn Bakker
Přispěvatelé: Damage and Repair in Cancer Development and Cancer Treatment (DARE), Stem Cell Aging Leukemia and Lymphoma (SALL), Translational Immunology Groningen (TRIGR), Groningen Research Institute for Asthma and COPD (GRIAC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Bradley, Allan [0000-0002-2349-8839], Apollo - University of Cambridge Repository
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Lymphoma
Aneuploidy
Chromosomal translocation
CHROMOSOMAL INSTABILITY
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Chromosome instability
Neoplasms
Leukaemia
Copy-number variation
Genetics
Mice
Knockout
Comparative Genomic Hybridization
Ecology
Karyotype
CANCER
3. Good health
SPINDLE-ASSEMBLY CHECKPOINT
Single-Cell Analysis
DNA Copy Number Variations
Biology
03 medical and health sciences
Genetic Heterogeneity
Behavior and Systematics
Copy number detection
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
medicine
Journal Article
Animals
Humans
AGING-ASSOCIATED PHENOTYPES
Ecology
Evolution
Behavior and Systematics
Whole genome sequencing
Chromosome Aberrations
ANEUPLOIDY
Research
Karyotype heterogeneity
Chromosome
Computational Biology
Cell Biology
medicine.disease
EVOLUTION
MICE
030104 developmental biology
Single cell sequencing
Single-cell sequencing
Software
Zdroj: Genome Biology, 17(1):115. BMC
Genome Biol. 17:115 (2016)
Genome Biology, 17. BioMed Central
Europe PubMed Central
Genome Biology
ISSN: 1465-6906
1474-7596
Popis: 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. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-0971-7) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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