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

Scientific Reports
Mahalakshmi KumaranSambasivarao Damaraju

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 iden...Continue Reading

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Citations

Jan 6, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Venzil Lavie DsouzaShama Prasada Kabekkodu

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Methods Mentioned

BETA
genotyping

Software Mentioned

GA
Partek® Genomics Suite
Genome Analyzer GA
Affymetrix
Golden Helix SNP and Variation suite
TargetScan
Ensembl
Genome Analyzer
Partek® Genomics [UNK]
UCSC

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