Skip to main content

Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility.

Publication ,  Journal Article
Piccolo, SR; Hoffman, LM; Conner, T; Shrestha, G; Cohen, AL; Marks, JR; Neumayer, LA; Agarwal, CA; Beckerle, MC; Andrulis, IL; Spira, AE ...
Published in: Mol Syst Biol
March 10, 2016

The signaling events that drive familial breast cancer (FBC) risk remain poorly understood. While the majority of genomic studies have focused on genetic risk variants, known risk variants account for at most 30% of FBC cases. Considering that multiple genes may influence FBC risk, we hypothesized that a pathway-based strategy examining different data types from multiple tissues could elucidate the biological basis for FBC. In this study, we performed integrated analyses of gene expression and exome-sequencing data from peripheral blood mononuclear cells and showed that cell adhesion pathways are significantly and consistently dysregulated in women who develop FBC. The dysregulation of cell adhesion pathways in high-risk women was also identified by pathway-based profiling applied to normal breast tissue data from two independent cohorts. The results of our genomic analyses were validated in normal primary mammary epithelial cells from high-risk and control women, using cell-based functional assays, drug-response assays, fluorescence microscopy, and Western blotting assays. Both genomic and cell-based experiments indicate that cell-cell and cell-extracellular matrix adhesion processes seem to be disrupted in non-malignant cells of women at high risk for FBC and suggest a potential role for these processes in FBC development.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Mol Syst Biol

DOI

EISSN

1744-4292

Publication Date

March 10, 2016

Volume

12

Issue

3

Start / End Page

860

Location

England

Related Subject Headings

  • Signal Transduction
  • Middle Aged
  • Leukocytes, Mononuclear
  • Humans
  • Genetic Variation
  • Genetic Predisposition to Disease
  • Gene Expression Profiling
  • Female
  • Cohort Studies
  • Cell Adhesion
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Piccolo, S. R., Hoffman, L. M., Conner, T., Shrestha, G., Cohen, A. L., Marks, J. R., … Bild, A. H. (2016). Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility. Mol Syst Biol, 12(3), 860. https://doi.org/10.15252/msb.20156506
Piccolo, Stephen R., Laura M. Hoffman, Thomas Conner, Gajendra Shrestha, Adam L. Cohen, Jeffrey R. Marks, Leigh A. Neumayer, et al. “Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility.Mol Syst Biol 12, no. 3 (March 10, 2016): 860. https://doi.org/10.15252/msb.20156506.
Piccolo SR, Hoffman LM, Conner T, Shrestha G, Cohen AL, Marks JR, et al. Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility. Mol Syst Biol. 2016 Mar 10;12(3):860.
Piccolo, Stephen R., et al. “Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility.Mol Syst Biol, vol. 12, no. 3, Mar. 2016, p. 860. Pubmed, doi:10.15252/msb.20156506.
Piccolo SR, Hoffman LM, Conner T, Shrestha G, Cohen AL, Marks JR, Neumayer LA, Agarwal CA, Beckerle MC, Andrulis IL, Spira AE, Moos PJ, Buys SS, Johnson WE, Bild AH. Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility. Mol Syst Biol. 2016 Mar 10;12(3):860.

Published In

Mol Syst Biol

DOI

EISSN

1744-4292

Publication Date

March 10, 2016

Volume

12

Issue

3

Start / End Page

860

Location

England

Related Subject Headings

  • Signal Transduction
  • Middle Aged
  • Leukocytes, Mononuclear
  • Humans
  • Genetic Variation
  • Genetic Predisposition to Disease
  • Gene Expression Profiling
  • Female
  • Cohort Studies
  • Cell Adhesion