Clinical & Experimental Metastasis

, Volume 27, Issue 5, pp 279–293

Dietary fat-dependent transcriptional architecture and copy number alterations associated with modifiers of mammary cancer metastasis

  • Ryan R. Gordon
  • Michele La Merrill
  • Kent W. Hunter
  • Peter Sørensen
  • David W. Threadgill
  • Daniel Pomp
Research Paper

Abstract

Breast cancer is a complex disease resulting from a combination of genetic and environmental factors. Among environmental factors, body composition and intake of specific dietary components like total fat are associated with increased incidence of breast cancer and metastasis. We previously showed that mice fed a high-fat diet have shorter mammary cancer latency, increased tumor growth and more pulmonary metastases than mice fed a standard diet. Subsequent genetic analysis identified several modifiers of metastatic mammary cancer along with widespread interactions between cancer modifiers and dietary fat. To elucidate diet-dependent genetic modifiers of mammary cancer and metastasis risk, global gene expression profiles and copy number alterations from mammary cancers were measured and expression quantitative trait loci (eQTL) identified. Functional candidate genes that colocalized with previously detected metastasis modifiers were identified. Additional analyses, such as eQTL by dietary fat interaction analysis, causality and database evaluations, helped to further refine the candidate loci to produce an enriched list of genes potentially involved in the pathogenesis of metastatic mammary cancer.

Keywords

Breast cancer Causality eQTL High-fat diet Tumors 

Abbreviations

AMD

Average metastasis density

C

Cis-acting eQTL

CNA

Copy number alteration

CNC

Copy number change

Chr

Chromosome

eQTL

Expression quantitative trait loci

G

Genetic alteration

HFD

High fat diet

IPA

Ingenuity pathway analysis

LRT

Likeihood ratio statistic

MCD

Matched control diet

MET

Metastasis detected at sacrifice

P

Phenotype

PyMT

Polyoma middle t oncoprotein

QTL

Quantitative trait loci

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Ryan R. Gordon
    • 1
    • 7
  • Michele La Merrill
    • 5
  • Kent W. Hunter
    • 6
  • Peter Sørensen
    • 8
  • David W. Threadgill
    • 2
    • 4
    • 7
  • Daniel Pomp
    • 1
    • 2
    • 3
    • 4
  1. 1.Department of NutritionUniversity of North Carolina Chapel HillChapel HillUSA
  2. 2.Department of GeneticsUniversity of North Carolina Chapel HillChapel HillUSA
  3. 3.Department of Cell and Molecular PhysiologyUniversity of North Carolina Chapel HillChapel HillUSA
  4. 4.Lineberger Comprehensive Cancer CenterUniversity of North Carolina Chapel HillChapel HillUSA
  5. 5.Department of Preventive MedicineMount Sinai School of MedicineNew YorkUSA
  6. 6.Laboratory of Cancer Biology & GeneticsNIH/NCIBethesdaUSA
  7. 7.Department of GeneticsNorth Carolina State UniversityRaleighUSA
  8. 8.Department of Genetics and Biotechnology, Faculty of Agricultural SciencesAarhus UniversityAarhusDenmark

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