Dissecting the clonal origins of childhood acute lymphoblastic leukemia by single-cell genomics.
Proc Natl Acad Sci U S A
; 111(50): 17947-52, 2014 Dec 16.
Article
em En
| MEDLINE
| ID: mdl-25425670
ABSTRACT
Many cancers have substantial genomic heterogeneity within a given tumor, and to fully understand that diversity requires the ability to perform single cell analysis. We performed targeted sequencing of a panel of single nucleotide variants (SNVs), deletions, and IgH sequences in 1,479 single tumor cells from six acute lymphoblastic leukemia (ALL) patients. By accurately segregating groups of cooccurring mutations into distinct clonal populations, we identified codominant clones in the majority of patients. Evaluation of intraclonal mutation patterns identified clone-specific punctuated cytosine mutagenesis events, showed that most structural variants are acquired before SNVs, determined that KRAS mutations occur late in disease development but are not sufficient for clonal dominance, and identified clones within the same patient that are arrested at varied stages in B-cell development. Taken together, these data order the sequence of genetic events that underlie childhood ALL and provide a framework for understanding the development of the disease at single-cell resolution.
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Base de dados:
MEDLINE
Assunto principal:
Variação Genética
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Genômica
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Análise de Célula Única
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article