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Small genomic insertions form enhancers that misregulate oncogenes
- Source :
- Nature Communications, Nature Communications, Vol 8, Iss 1, Pp 1-13 (2017), Nature
- Publication Year :
- 2016
-
Abstract
- The non-coding regions of tumour cell genomes harbour a considerable fraction of total DNA sequence variation, but the functional contribution of these variants to tumorigenesis is ill-defined. Among these non-coding variants, somatic insertions are among the least well characterized due to challenges with interpreting short-read DNA sequences. Here, using a combination of Chip-seq to enrich enhancer DNA and a computational approach with multiple DNA alignment procedures, we identify enhancer-associated small insertion variants. Among the 102 tumour cell genomes we analyse, small insertions are frequently observed in enhancer DNA sequences near known oncogenes. Further study of one insertion, somatically acquired in primary leukaemia tumour genomes, reveals that it nucleates formation of an active enhancer that drives expression of the LMO2 oncogene. The approach described here to identify enhancer-associated small insertion variants provides a foundation for further study of these abnormalities across human cancers.<br />United States. National Institutes of Health (HG002668)<br />United States. National Institutes of Health (CA109901)
- Subjects :
- 0301 basic medicine
Adult
Adolescent
Somatic cell
Science
General Physics and Astronomy
Biology
medicine.disease_cause
Genome
Article
General Biochemistry, Genetics and Molecular Biology
DNA sequencing
03 medical and health sciences
chemistry.chemical_compound
Young Adult
hemic and lymphatic diseases
Cell Line, Tumor
medicine
Humans
Leukemia-Lymphoma, Adult T-Cell
Enhancer
Child
Genetics
Multidisciplinary
Base Sequence
Gene Expression Regulation, Leukemic
Genome, Human
Mutagenesis
Infant
Reproducibility of Results
General Chemistry
Oncogenes
Corrigenda
3. Good health
Mutagenesis, Insertional
030104 developmental biology
Enhancer Elements, Genetic
chemistry
Child, Preschool
Human genome
Carcinogenesis
DNA
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Nature communications
- Accession number :
- edsair.doi.dedup.....8ad1229288c1f3742380f1418d9f24e3