Highly mutable core promoters in triple-negative breast cancer

UM > Faculty of Health Sciences > DEPARTMENT OF PUBLIC HEALTH AND MEDICINAL ADMINISTRATION

Status	即將出版Forthcoming
	Highly mutable core promoters in triple-negative breast cancer
	Wang, S. M.
Source Publication	Genes and Diseases
ISSN	2352-3042
Abstract	Abnormal gene expression plays key role in cancer development. A core promoter is located around the transcriptional start site. Through interaction between core promoter sequences and trans-transcriptional factors, core promoter controls transcriptional initiation. We hypothesized that in cancer, core promoter sequences could be mutated to interfere the interaction with transcriptional factors, resulting in altered transcriptional initiation and abnormal gene expression and cancer development. We used triple-negative breast cancer (TNBC) as a model to test our hypothesis. We collected genome-wide core promoter variants from 279 TNBC genomes. After extensive filtering of normal genomic polymorphism, we identified 19,427 recurrent somatic variants in 1,238 core promoters of 1,274 genes and 1,694 recurrent germline variants in 272 core promoters of 294 genes. Many of the affected genes were oncogenes and tumor suppressors. Analysis of RNA-seq data from the same patient cohort identified increased or decreased gene expression in 439 somatic and 85 germline variants-affected genes, and the results were validated by luciferase reporter assay. By comparing with the core promoter variation data from 610 unclassified breast cancer, we observed that core promoter variants in TNBC were highly TNBC-specific. We further identified 271 drugs targeting 39 increasingly expressed genes with somatic core promoter variants and 34 drugs targeting 8 increasingly expressed genes with germline core promoter variants. Our study demonstrates that core promoter is highly mutable in cancer, and can play etiological roles in TNBC and other types of cancer through influencing transcriptional initiation.
Keyword	promoter mutation cancer expression
Language	英語English
The Source to Article	PB_Publication
PUB ID	60476
Document Type	Journal article
Collection	DEPARTMENT OF PUBLIC HEALTH AND MEDICINAL ADMINISTRATION
Recommended Citation GB/T 7714	Wang, S. M.. Highly mutable core promoters in triple-negative breast cancer[J]. Genes and Diseases.
APA	Wang, S. M..Highly mutable core promoters in triple-negative breast cancer. Genes and Diseases.
MLA	Wang, S. M.."Highly mutable core promoters in triple-negative breast cancer".Genes and Diseases .

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