Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

Marie-Christine Pouliot  1 , Charu Kothari  1 , Charles Joly-Beauparlant  1 , Yvan Labrie  1 , Geneviève Ouellette  1 , Jacques Simard  1 , Arnaud Droit  1 , Francine Durocher  1
Affiliations

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

Marie-Christine Pouliot et al. Oncotarget. .

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.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1. Principal component analysis (PCA) on lymphoblastoid cell lines
Unsupervised classification of the groups using a combination of PC1, PC2 and PC3. Distance between dots is a dimensional measure for the similarity of the expression profiles of the samples (red: BRCA1, blue: BRCA2, green: BRCAX unaffected and purple: BRCAX affected).
Figure 2
Figure 2. Hierarchical clustering of the 95 transcripts differentially expressed
Unsupervised LCLs classification based on the significantly and differentially expressed transcripts measured by RNA-sequencing using bonferroni corrected p-value <0.01. Color bar represents each of our groups (red: BRCA1, blue: BRCA2, Green: BRCAX) and status of disease (pink: affected and white: unaffected).
Figure 3
Figure 3. Venn diagram of significantly and differentially expressed transcripts compared with BRCAX unaffected individuals
An intersectional analysis of differentially expressed transcripts compared with BRCAX unaffected was performed. The cut-off value was Bonferroni corrected p-value ≤ 0.01.
Figure 4
Figure 4. Hierarchical clustering of the 28 transcripts differentially expressed between BRCAX affected and BRCAX unaffected individuals
Heat map of the TPM (Transcripts Per Million) for 32 women using Euclidean distance with average linkage.
See this image and copyright information in PMC

References

    1. Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian Cancer Statistics 2014. Toronto, ON; 2014. 1 p.
    1. Peto J, Houlston RS. Genetics and the common cancers. Eur J Cancer. 2001;37:S88–96. https://doi.org/10.1016/S0959-8049(01)00255-6. - DOI - PubMed
    1. Collaborative Group on Hormonal Factors in Breast Cancer Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53297 women with breast cancer and 100239 women without breast cancer from 54 epidemiological studies. Lancet. 1996;347:1713–27. https://doi.org/10.1016/S0140-6736(96)90806-5. - DOI - PubMed
    1. Aloraifi F, McCartan D, McDevitt T, Green AJ, Bracken A, Geraghty J. Protein-truncating variants in moderate-risk breast cancer susceptibility genes: a meta-analysis of high-risk case-control screening studies. Cancer Genet. 2015;208:455–63. https://doi.org/10.1016/j.cancergen.2015.06.001. - DOI - PubMed
    1. Easton DF. How many more breast cancer predisposition genes are there? Breast Cancer Res. 1999;1:14–7. https://doi.org/10.116:bcr6. - PMC - PubMed