Breast cancer associated germline structural variants harboring small noncoding RNAs impact post-transcriptional gene regulation

Abstract Copy Number Variants (CNVs) are a class of structural variations of DNA. Germline CNVs are known to confer disease susceptibility, but their role in breast cancer warrants further investigations. We hypothesized that breast cancer associated germline CNVs contribute to disease risk through...

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Autores principales:	Mahalakshmi Kumaran, Preethi Krishnan, Carol E. Cass, Roland Hubaux, Wan Lam, Yutaka Yasui, Sambasivarao Damaraju
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0a8aab14164b4afaaa9d425c68417891
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spelling	oai:doaj.org-article:0a8aab14164b4afaaa9d425c684178912021-12-02T12:32:22ZBreast cancer associated germline structural variants harboring small noncoding RNAs impact post-transcriptional gene regulation10.1038/s41598-018-25801-12045-2322https://doaj.org/article/0a8aab14164b4afaaa9d425c684178912018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25801-1https://doaj.org/toc/2045-2322Abstract Copy Number Variants (CNVs) are a class of structural variations of DNA. Germline CNVs are known to confer disease susceptibility, but their role in breast cancer warrants further investigations. We hypothesized that breast cancer associated germline CNVs contribute to disease risk through gene dosage or other post-transcriptional regulatory mechanisms, possibly through tissue specific expression of CNV-embedded small-noncoding RNAs (CNV-sncRNAs). Our objectives are to identify breast cancer associated CNVs using a genome wide association study (GWAS), identify sncRNA genes embedded within CNVs, confirm breast tissue (tumor and normal) expression of the sncRNAs, correlate their expression with germline copy status and identify pathways influenced by the genes regulated by sncRNAs. We used an association study design and accessed germline CNV data generated on Affymetrix Human SNP 6.0 array in 686 (in-house data) and 495 (TCGA data) subjects served as discovery and validation cohorts. We identified 1812 breast cancer associated CNVs harboring miRNAs (n = 38), piRNAs (n = 9865), snoRNAs (n = 71) and tRNAs (n = 12) genes. A subset of CNV-sncRNAs expressed in breast tissue, also showed correlation with germline copy status. We identified targets potentially regulated by miRNAs and snoRNAs. In summary, we demonstrate the potential impact of embedded CNV-sncRNAs on expression and regulation of down-stream targets.Mahalakshmi KumaranPreethi KrishnanCarol E. CassRoland HubauxWan LamYutaka YasuiSambasivarao DamarajuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mahalakshmi Kumaran Preethi Krishnan Carol E. Cass Roland Hubaux Wan Lam Yutaka Yasui Sambasivarao Damaraju Breast cancer associated germline structural variants harboring small noncoding RNAs impact post-transcriptional gene regulation
description	Abstract Copy Number Variants (CNVs) are a class of structural variations of DNA. Germline CNVs are known to confer disease susceptibility, but their role in breast cancer warrants further investigations. We hypothesized that breast cancer associated germline CNVs contribute to disease risk through gene dosage or other post-transcriptional regulatory mechanisms, possibly through tissue specific expression of CNV-embedded small-noncoding RNAs (CNV-sncRNAs). Our objectives are to identify breast cancer associated CNVs using a genome wide association study (GWAS), identify sncRNA genes embedded within CNVs, confirm breast tissue (tumor and normal) expression of the sncRNAs, correlate their expression with germline copy status and identify pathways influenced by the genes regulated by sncRNAs. We used an association study design and accessed germline CNV data generated on Affymetrix Human SNP 6.0 array in 686 (in-house data) and 495 (TCGA data) subjects served as discovery and validation cohorts. We identified 1812 breast cancer associated CNVs harboring miRNAs (n = 38), piRNAs (n = 9865), snoRNAs (n = 71) and tRNAs (n = 12) genes. A subset of CNV-sncRNAs expressed in breast tissue, also showed correlation with germline copy status. We identified targets potentially regulated by miRNAs and snoRNAs. In summary, we demonstrate the potential impact of embedded CNV-sncRNAs on expression and regulation of down-stream targets.
format	article
author	Mahalakshmi Kumaran Preethi Krishnan Carol E. Cass Roland Hubaux Wan Lam Yutaka Yasui Sambasivarao Damaraju
author_facet	Mahalakshmi Kumaran Preethi Krishnan Carol E. Cass Roland Hubaux Wan Lam Yutaka Yasui Sambasivarao Damaraju
author_sort	Mahalakshmi Kumaran
title	Breast cancer associated germline structural variants harboring small noncoding RNAs impact post-transcriptional gene regulation
title_short	Breast cancer associated germline structural variants harboring small noncoding RNAs impact post-transcriptional gene regulation
title_full	Breast cancer associated germline structural variants harboring small noncoding RNAs impact post-transcriptional gene regulation
title_fullStr	Breast cancer associated germline structural variants harboring small noncoding RNAs impact post-transcriptional gene regulation
title_full_unstemmed	Breast cancer associated germline structural variants harboring small noncoding RNAs impact post-transcriptional gene regulation
title_sort	breast cancer associated germline structural variants harboring small noncoding rnas impact post-transcriptional gene regulation
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/0a8aab14164b4afaaa9d425c68417891
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_version_	1718394078466408448

Breast cancer associated germline structural variants harboring small noncoding RNAs impact post-transcriptional gene regulation

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