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Oncotarget. 2017 Aug 12;8(45):78691-78712. doi: 10.18632/oncotarget.20219. eCollection 2017 Oct 3.

Transcriptional signature of lymphoblastoid cell lines of BRCA1, BRCA2 and non-BRCA1/2 high risk breast cancer families.

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1
CHU de Québec Research Centre-Université Laval, Department of Molecular Medicine, Québec, Canada.

Abstract

Approximately 25% of hereditary breast cancer cases are associated with a strong familial history which can be explained by mutations in BRCA1 or BRCA2 and other lower penetrance genes. The remaining high-risk families could be classified as BRCAX (non-BRCA1/2) families. Gene expression involving alternative splicing represents a well-known mechanism regulating the expression of multiple transcripts, which could be involved in cancer development. Thus using RNA-seq methodology, the analysis of transcriptome was undertaken to potentially reveal transcripts implicated in breast cancer susceptibility and development. RNA was extracted from immortalized lymphoblastoid cell lines of 117 women (affected and unaffected) coming from BRCA1, BRCA2 and BRCAX families. Anova analysis revealed a total of 95 transcripts corresponding to 85 different genes differentially expressed (Bonferroni corrected p-value <0.01) between those groups. Hierarchical clustering allowed distinctive subgrouping of BRCA1/2 subgroups from BRCAX individuals. We found 67 transcripts, which could discriminate BRCAX from BRCA1/BRCA2 individuals while 28 transcripts discriminate affected from unaffected BRCAX individuals. To our knowledge, this represents the first study identifying transcripts differentially expressed in lymphoblastoid cell lines from major classes of mutation-related breast cancer subgroups, namely BRCA1, BRCA2 and BRCAX. Moreover, some transcripts could discriminate affected from unaffected BRCAX individuals, which could represent potential therapeutic targets for breast cancer treatment.

KEYWORDS:

RNA-seq; gene expression; hereditary breast cancer; high-risk BRCA1/2/X families; lymphoblastoid cell lines

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