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Sequencing of Coding and Non-coding Regions in Primary Breast Cancers and Patient-matched Controls

ABSTRACT:

Genomic analysis of tumor samples has led to the identification of hundreds of cancer genes based on the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here, we performed deep sequencing in 360 primary breast cancers and developed computational methods to identify significantly mutated promoters. Clear signals were found in the promoters of four genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbors a mutational hotspot in its promoter that leads to overexpression through increased E2F binding. RMRP and NEAT1, two non-coding RNA genes, carry mutations that alter protein binding to the promoter and impact expression levels. Overall, our study shows that recurrent mutations in or near gene promoters in cancers have functional consequences. Power analyses indicate that more such genes remain to be discovered through deep sequencing of adequately sized patient cohorts.

PROVIDER: phs001250 | dbGaP |

SECONDARY ACCESSION(S): PRJNA353974PRJNA353973

REPOSITORIES: dbGaP

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			Action	DRS
	GapExchange_phs001250.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	Study_Report.phs001250.PrimaryBreastCancers.v1.p1.MULTI.pdf	Pdf
	manifest_phs001250.PrimaryBreastCancers.v1.p1.c1.GRU.pdf	Pdf
	manifest_phs001250.PrimaryBreastCancers.v1.p1.c2.DS-CA-MDS.pdf	Pdf

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